Morphological Changes In Renal Tissue Research Articles

#1227 The role of P-selectin (CD62P) expression in renal tissue in the development of diabetic nephropathy

Abstract Background and Aims The prevalence of diabetic nephropathy (DN) is increasing in line with the increase in the incidence of diabetes mellitus (DM) worldwide. The latest data from the International Diabetes Federation (IDF) predicts that by 2045, more than 10.5% of adults worldwide will have diabetes. This will lead to kidney damage in 100-250 million people. DN is characterized by structural and functional changes. As a result of chronic hyperglycemia, pathogenic changes in the vascular wall develop, and the frequency of micro- and macrovascular complications associated with morbidity and mortality among patients with diabetes increases. However, the exact mechanism of vascular complications is not completely clear. Endothelial dysfunction plays a key role in triggering the development of inflammatory mechanisms that are associated with vascular complications in patients with type 2 diabetes mellitus (T2DM). Activation of the endothelium due to increased release of cytokines and expression of adhesion molecules promotes platelet activation and their adhesion to the activated endothelium. Selectins (E-selectin, L-selectin and P-selectin) play a major role in the development of microvascular complications. The aim of the study was to examine the role of P-selectin (CD62p) expression in the glomerular endothelium and peritubular capillaries in patients with different morphological classes of DN and to evaluate its effect on the development and progression of morphological changes in renal tissue. Method Was examined 49 patients with T2DM complicated by the development of DN. The average age of the patients was 66.58 ± 3.27 years. There were 35 women, 14 men. The duration of the disease was 17.70 ± 0.35 years. The duration of DN from the moment of detection of microalbuminuria to the morphological examination of the renal tissue and diagnosis was 1.65 ± 0.34 years. All patients underwent light and immunofluorescence microscopy of kidney tissue biopsies obtained by intravital puncture biopsy. Morphological changes in tissue were assessed in accordance with the latest international classification of diabetic nephropathy developed by the Scientific Committee of the Pathology Society, USA. According to light microscopy data, class IIa (mild mesangial expansion) was detected in 12 patients, class IIb (severe mesangial expansion) in 14 patients, class III (Kimmelstil–Wilson nodular lesions) in 19 patients, and class IV (advanced diabetic glomerulosclerosis) in 5 patients. In addition to light microscopy, the expression of CD62β (P-selectin) in the glomerular endothelium and in peritubular capillaries was determined in all patients. FITc-labeled monoclonal antibodies (FITC anti-human CD62p Antibody, clone AK4 Cat#304904), were used (Biolegend, USA). Results Analysis of biopsy tissue from DN patients showed that CD62p expression is detected both in the glomerular endothelium (1.6383 ± 0.4789 (95% CI: 0.9574-2.7234)) and in peritubular capillaries (1.1702 ± 0.1308 (95% CI: 0.9149–1.4250)). Using the linear regression method with the calculation of the coefficients of determination R2 (R Square), the values of the F criterion, significant regression models were obtained: Expression of CD62p in the glomerular endothelium promotes the development and progression of arteriolar hyalinosis (R2=0.213, F=12.476 p=0.001); expansion of the mesangial matrix (R2=0.362, F=26.09, p=0.0001); thickening of the basement membrane (R2=0.127, F=6.57, p=0.014); development and progression of nodular Kimmelstiel–Wilson lesions (R2=0.106, F=5.360, p=0.025). Expression of CD62p in peritubular capillaries promotes the development of interstitial sclerosis (R2=0.549, F=54.732, p=0.0001). The severity of CD62p expression in the glomerular endothelium depends on the morphological class of DN in patients (R2=0.216, F=12.684, p=0.001). Conclusion

Rehmannia glutinosa Libosch and Cornus officinalis Sieb herb couple ameliorates renal interstitial fibrosis in CKD rats by inhibiting the TGF-β1/MAPK signaling pathway

Ethnopharmacological relevanceHerb couple Rehmannia glutinosa Libosch and Cornus officinalis Sieb (RC), originated from "Liuwei Dihuang Pill" which recorded in Key to Therapeutics of Children's Diseases. Traditionally, they have been used widely for their ability to nourish yin and energize the kidneys. Our previous study indicated that the RC could protect against adenine induced Chronic kidney disease (CKD) rats. Nevertheless, there is still no clear explanation of the mechanisms by which RC affects renal interstitial fibrosis in CKD rats. Aim of the studyCurrent Work aims to explore the amelioration and potential mechanism of RC on renal interstitial fibrosis in CKD rats. Materials and methodsCKD rats were induced by adenine. Two weeks after administration, blood, urine, and kidney tissue were collected for biochemical analysis. Observing the physiological state of rats through the changes of rat body weight and renal index. The pro-inflammatory cytokines were measured by enzyme linked immunosorbent assay (ELISA), while renal tissue damage and fibrosis were assessed with Hematoxylin-eosin staining (H&E) and Masson's trichrome staining. In order to determine the levels of indicators and proteins associated with fibrosis signaling pathways, real time PCR (Rt-PCR), Western blot (WB), and immunofluorescence were employed. ResultsThe renal interstitial fibrosis led to impaired cellular functions with increased the levels of Blood Urea Nitrogen (BUN), Urine protein (UP), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α). and simultaneous up-regulated collagenⅠ(COL-1), fibronection (FN), α-smooth muscle actin (a-SMA), transforming growth factor-β1 (TGF-β1), c-Jun N-terminal kinase (JNK), p38 and extracellular regulated protein kinases (ERK), down-regulated the expression of the E-cadherin proteins. RC notably improved renal dysfunction in CKD rats as indicated by decreases in BUN, UP, and renal index. In addition, consistent with the morphological changes of renal tissue, renal interstitial fibrosis in CKD rats after RC intervention was significantly improved, mainly manifested by a decrease in the positive expression of COL-1, FN, and a-SMA, and increased levels of E-cadherin protein. Meanwhile, RC reduced the classical pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in adenine-induced CKD rats. Additionally, RC administration also down-regulated TGF-β1, JNK, p38 and ERK. ConclusionIn conclusion, RC may reduce inflammation in adenine induced CKD rats, improve extracellular matrix (ECM) components deposition, and diminish epithelial-mesenchymal transition (EMT) marker protein levels. Furthermore, RC intervention significantly reduces the release of inflammatory cytokines and inhibits the TGF-β1/MAPK signaling pathway. Based on the results, RC might be useful in the treatment of adenine induced renal fibrosis.

Study on the Effects of Melatonin on Cisplatin-Induced Apoptosis of Renal Tubular Epithelial Cells and Autophagy Protein L Light Chain 3 (LC3)

Purpose: The aim of this work was to discuss Melatonin’s effects on Cisplatin-induced Apoptosis of Renal Tubular Epithelial Cells. Materials and Methods: Blood and renal tissue were collected, The level of serum creatinine (Scr) was detected, the content of p53 protein in renal tissue was detected by immunohistochemistry, the expression of p53 protein and autophagy marker protein microtubule associated protein L light chain 3II (LC3II)/LC 3I ratio in renal tissue was detected by WB method, the apoptosis of renal tubular epithelial cells was detected by TUNEL method, and the morphological changes of renal tissue were observed by light microscope. Results: Scr level and apoptosis cell rate were significantly increased in Model group (P < 0.001), P53 and LC 3II/LC 3I ratio were significantly depressed (P < 0.001). With MT supplement, Scr level and apoptosis cell rate were significantly depressed (P < 0.05); MT could significantly up-regulate P53 and LC 3II/LC 3I ratio (P < 0.05), MT could improve the pathological changes such as renal tubular epithelial cell fusion and vacuolar degeneration, and reduce renal tubular injury. Conclusion: MT has a protective effect on cisplatin induced AKI in mice. Its mechanism may be related to up regulating the expression levels of p53 protein and LC 3II/LC 3I ratio.

Comparative analysis of morphological changes in renal tissue under the influence of light desynchronosis

AIM: To compare morphological changes that occur in renal tissue, as a result of exposure to various models of light desynchronosis.
 MATERIAL AND METHODS: This study was conducted on 48 white rats. Three experimental groups were exposed to light for 21 days. The LL (0:24) model was studied in the first group, while the LD 18:6 and 12:10 models were studied in the second and third groups, respectively. The control group was kept in natural conditions all through the experiment.
 The animals were placed under anesthesia with a combination of Telazol (ZoetisInc, USA) and Xylanit (Nita-farm, Russia). Afterward, their right kidney was removed. The samples obtained were prepared according to the standard method. Statistical processing was performed using the package of applied statistical programs "STATISTICA 10" (StatSoft , USA).
 RESULTS: Morphological disorders of the renal tissue were observed in the three experimental groups. In the first experimental group, there was a significant segmentation of the glomeruli, accompanied by dystrophic changes in the renal tubules. In the second experimental group, glomerular segmentation was more pronounced. In the renal tissue of animals of the third experimental group, the disorders were highly observable, and the sclerotized segment is noted. Changes in morphometric indicators were significant across all experimental groups.
 CONCLUSION: Desynchronosis harms the renal tissue by causing changes in its morphology. The most significant disorders characterized by sclerosis were observed in the kidneys of animals in the third experimental group.

Peroxisome Proliferator-Activated Receptor Gene Knockout Promotes Podocyte Injury in Diabetic Mice

Objective To investigate the effects of peroxisome proliferator-activated receptor (PPARγ) expression on renal podocyte in diabetic mice by conditionally knockout mouse PPARγ gene. Methods Wild-type C57BL mice and PPARγ gene knockout mice were used as research objects to establish the diabetic mouse model, which was divided into normal control group (NC group), normal glucose PPARγ gene knockout group (NK group), diabetic wild-type group (DM group), and diabetic PPARγ gene knockout group (DK group), with 8 mice in each group. After 16 weeks, the mice were sacrificed for renal tissue collection. Morphological changes of renal tissue were observed by HE and Masson staining, and ultrastructure of renal tissue was observed by transmission electron microscope. Protein expressions of PPARγ, podocin, nephrin, collagen IV, and fibronectin (FN) in renal tissues were detected by immunohistochemistry and Western blot, and mRNA changes of PPARγ, podocin, and nephrin in renal tissues were detected by qRT-PCR. Results Compared with the NC group, the protein and mRNA expressions of PPARγ, podocin, and nephrin decreased in the kidney tissue of mice in the DM group, while the protein expressions of collagen IV and FN increased. The expression of various proteins in kidney tissues of the DK group was consistent with that of the DM group, and the difference was more obvious. The expression of PPARγ protein and mRNA decreased in the NK group, while the expression of podocin, nephrin protein and mRNA, collagen IV, and FN protein showed no significant difference. Conclusion In diabetic renal tissue, the loss of PPARγ can aggravate podocellular damage and thus promote the occurrence of diabetic renal fibrosis. Increasing the expression of PPARγ may effectively relieve renal podocyte impairment in diabetic patients, which can be used for the treatment of diabetic nephropathy.

The effect of modulators of hydrogen sulfide metabolism on morphological changes in kidneys of rats with high-calorie diet-induced obesity

Annotation. Obesity is one of the factors in the development of chronic kidney disease. Hydrogen sulfide (H2S) plays an important role in regulating the functional state of the kidneys, and its endogenous production is disrupted in obesity. The search for effective and safe correctors of H2S metabolism in the kidneys in obesity is relevant. The aim of the study was to establish the effect of potential modulators of H2S metabolism on biochemical and morphological changes in the kidneys of rats with high-calorie-diet-induced obesity (DIO). The experiments were performed on 60 white male laboratory rats in accordance with the principles of bioethics (Strasbourg, 1986; Kyiv, 2001). DIO was modeled using a high-calorie high-fat diet (39.5% fat per calorie). Metabolic correction was performed with H2S metabolism modulators (zinc sulfate, sodium thiosulfate, lipoic acid, taurine). Control rats received a standard diet (10.5% fat per calorie). Somatometric parameters, H2S level, morphological changes of kidney tissue were determined. Statistical processing was performed in the package IBM Statistics SPSS 26, differences were assessed in the Kruskel-Wallis test at a significance level of p<0.05. It was found that the development of DIO was accompanied by a decrease in the concentration of H2S in the kidneys (1.9 times, p<0.001), characteristic morphological changes in renal tissue with damage of the glomerular and tubular apparatus, severe inflammatory reaction of the parenchyma, endothelial damage and vascular structure. All metabolic correctors increased the level of H2S in the kidneys and inhibited the progression of nephropathy under the conditions of DIO. Zinc sulfate and lipoic acid were the most effective in preserving the structural elements of the renal parenchyma, while sodium thiosulfate and taurine were less effective.

MO609: Intrarenal TNF-α Expression in The Development of Diabetic Nephropathy

Abstract BACKGROUND AND AIMS Diabetic nephropathy (DN) develops in 40%–60% of people with type 2 diabetes mellitus (DM) and is characterized by a progressive and persistent decline in renal function, being the main cause of end-stage renal disease worldwide. TNF-α plays an important role in the development of inflammation, can lead to the destruction of connective tissue, release of lytic enzymes, has a direct effect on the processes of tissue regeneration, changing the expression of collagen types I, III and V. Also, TNF-α stimulates an increase in the synthesis of endothelin-1 by glomerular mesangial cells and has a direct cytotoxic effect on renal tissue, and increased cytokine production induces the processes of apoptosis and necrosis of glomerular cells. The aim of this work was to study the role of intrarenal TNF-α expression in the development of morphological changes in renal tissue in DN patients. METHOD We examined 50 patients with type 2 diabetes (mean age 66.58 ± 3.27 years). The duration of DM is 17.69 ± 0.35 years, and the duration of DN from the moment of detection of albuminuria to morphological examination of the renal tissue and diagnosis is 1.63 ± 0.34 years. Light and immunofluorescence microscopy of biopsy specimens of renal tissue of patients was carried out. Morphological changes were assessed in accordance with the Pathologic Classification of Diabetic Nephropathy (2010). According to light microscopy, 12 patients had class IIa (mild mesangial expansion), 13 patients had class IIb (severe mesangial expansion), 19 patients had class III (Kimmelstiel–Wilson nodular lesions) and 5 patients had class IV (extended diabetic glomerulosclerosis). In all patients, TNF-α expression in the glomerulus and in the interstitium was determined by immunofluorescence microscopy. RESULTS Correlation analysis showed the effect of TNF-α expression in the glomerulus in class IIa on the development of segmental sclerosis of the glomeruli (P = 0.04). A decrease in TNF-α expression in the glomerulus is accompanied by periglomerular sclerosis (P = 0.012), and also increases: thickening of the glomerular basement membrane (P = 0.03), expansion of the mesangium passes from soft to severe and affects more than 25% of the mesangial matrix (IIb stage) (P = 0.033), Kimmelstiel–Wilson nodular lesions are formed (P = 0.009). The interstitial expression of TNF-α remains high in the epithelium of the urinary tubules and in the interstitial cells of the kidney, regardless of the DN class and influences the development of tubulointerstitial fibrosis (P = 0.003). In order to clarify the prognostic significance of TNF-α and its role in the progression of DN, a linear regression analysis was carried out with the calculation of the coefficients of determination R2 (R Square) and using the Durban–Watson test and analysis of variance (ANOVA "Analysis of Variance") using the F criterion and calculating the standardized beta coefficient (ß) with a 95% confidence interval. It has been shown that glomerular expression of TNF-α affects the following: (i) progression of the expansion of the mesangial matrix (F = 4.817, P = 0.033; β = –0.311; CI –0.506 to –0.22, P = 0.033); (ii) the formation of Kimmelstiel–Wilson nodular lesions (F = 5.383, P = 0.025; β = –0.327; CI –1.375 to –0.97, P = 0.025). Interstitial expression of TNF-α contributes to the following: (i) the progression of arterial hyalinosis (F = 4.349, P = 0.043; β = 0.297; CI 0.009–0.497, P = 0.043); (ii) interstitial sclerosis (F = 9.541, P = 0.003; β = 0.422; CI 0.101–0.479, P = 0.003). CONCLUSION

VEGF-C — a biomarker of renal injury in the experimental model of intra-abdominal hypertension

Lymphangiogenesis plays an important role in development of renal parenchyma inflammation during kidney injury. Vascular endothelial growth factor type C (VEGF-C), cytokine that regulates lymphangiogenesis, is a potential early biomarker for acute kidney injury. Aim. To study the concentration of VEGF-C in renal homogenate and blood serum of newborn rats with experimental intraabdominal hypertension (IAH) of varying severity and duration, to establish a relationship with morphological changes in the renal tissue. Materials and methods. The experiment was conducted on 50 newborn Wistar rats. Rats were divided into 5 groups of 10 rats each: groups 1 and 2 with mild IAH lasting 5 and 10 days, respectively, and groups 3 and 4 with severe IAH lasting 5 and 10 days, respectively, and the control group. IAH was modelled by injecting sterile vaseline into the abdominal cavity to a predetermined level of IAH under the control of intra-vesical manometry. VEGF-C content was measured by ELISA. Morphological examination of the biopsy material and its photography were carried out using a Leica DM2000 microscope. The Mann—Whitney, Kruskal—Wallis, Wilcoxon tests, as well as one-way ANOVA, were used for statistical analysis. Results. The level of VEGF-C in the renal homogenate was increased in all groups (pc < 0.001); the degree of VEGF-C increase depended on the severity of IAH (p < 0.05) but not on the duration of IAH exposure. The VEGF-C blood serum level was increased only in group 3 (pc = 0.011). Morphological analysis showed hydropic dystrophy: changes in the height of the tubular epithelium, an increase in interstitial edema, expansion of the urinary spaces of glomeruli. The degree of morphological changes depended on the severity and duration of IAH. Conclusion. Changes in VEGF-C level assessed in the renal homogenate correlated with morphological changes in renal tissue of rats with different severity and duration of IAH.

The role of adhesion molecule expression in the development of morphological changes in renal tissue in patients with type 2 diabetes

The role of adhesion molecule expression in the development of morphological changes in renal tissue in patients with type 2 diabetes

Exploration about the protection mechanism of 5-hydroxy-1-methylhydantoin on paraquat poisoning model

To investigate the effects of 5-hydroxy-1-methylhydantoin (HMH) on kidney injury induced by paraquat (PQ). Fifteen SPF healthy Kunming mice were randomly divided into normal saline (NS) control group, PQ poisoning model group and HMH intervention group, with 5 mice in each group. PQ poisoning model was challenged by one-time gavage of 30 mg/kg PQ solution. The NS group received the same amount of NS by gavage. The HMH group was given 100 mg/kg of HMH immediately after the model was made and continued to be gavaged. Mice in each group were sacrificed 1 day after HMH gavage and heart blood and renal tissue were harvested for examination. The morphological changes of renal tissue were observed under light microscope by hematoxylin-eosin (HE) staining. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in renal tissue were detected according to the instructions of the kit. The expression of heme oxygenase-1 (HO-1) and interleukin-1β (IL-1β) in renal tissues were detected by Western Blot. The serum metabolites were detected by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), the overall distribution of each sample was observed by principal component analysis (PCA), the accuracy of the model was evaluated by multidimensional analysis orthogonal partial least squares-discriminant analysis (OPLS-DA), and the difference metabolites were screened by variable importance in the projection (VIP) value > 1. Light microscopic observation showed that: glomerular structure in NS group was clear, there was no hyperemia and inflammatory cell infiltration in renal interstitium and blood vessels. In PQ group, some glomeruli atrophy and necrosis, capillary congestion in glomeruli, infiltration of inflammatory cells around glomeruli, swelling of renal tubular epithelial cells, slight stenosis of lumen, and occasional necrosis and exfoliation of epithelial cells occurred. The degree of kidney injury in HMH group was significantly less than that in PQ group. Compared with the NS group, the content of MDA in the PQ group was significantly increased (nmol/g: 6.70±0.84 vs. 2.70±0.43, P < 0.01) and the activity of SOD was significantly decreased (kU/L: 33.30±4.66 vs. 50.20±3.23, P < 0.05), the protein expression of HO-1 and IL-1β were significantly increased (HO-1/β-actin: 1.11±0.12 vs. 0.61±0.13, IL-1β/β-actin: 0.93±0.13 vs. 0.32±0.06, both P < 0.05). Compared with the PQ group, the content of MDA in the HMH group was significantly decreased (nmol/g: 5.10±0.93 vs. 6.70±0.84, P < 0.05) and the activity of SOD was significantly increased (kU/L: 61.00±9.02 vs. 33.30±4.66, P < 0.05), the protein expression of HO-1 was significantly decreased (HO-1/β-actin: 0.77±0.07 vs. 1.11±0.12, P < 0.05), however, there was no significant difference in the protein expression of IL-1β (IL-1β/β-actin: 0.87±0.13 vs. 0.93±0.13, P > 0.05). Metabolite detection results showed that: compared with NS group, the levels of creatinine, glycine, succinic acid, fumaric acid and citric acid were significantly increased in the PQ group (VIP value was 1.50, 1.58, 1.64, 1.74 and 1.95 respectively, all P < 0.05), while the levels of palmitic acid,α-tocopherol and 6-phosphogluconic acid were significantly decreased (VIP value was 1.10, 1.55 and 1.56 respectively, all P < 0.05). Compared with the PQ group, the levels of creatinine and citric acid were significantly decreased in the HMH group (VIP value was 1.50 and 1.86, both P < 0.05), while trans-4-hydroxy-proline, D-glyceric acid, 2, 6-fructose phosphate, 6-phosphate gluconic acid and aminomalonic acid were significantly increased (VIP value was 1.36, 1.55, 1.63, 1.68 and 1.76 respectively, all P < 0.05). HMH protects kidney injury caused by PQ poisoning by correcting tricarboxylic acids cycle disturbance, lipid peroxidation and energy metabolism disturbance, and its mechanism is related to the regulation of HO-1 protein expression through Nrf2 pathway.

POSTPARTUM ATYPICAL HEMOLYTIC UREMIC SYNDROME. CLINICAL OBSERVATIONS AND HISTOLOGICAL FEATURES

Described two clinical observations of atypical hemolytic-uremic syndrome (AHUS) in patients in the second and third trimesters of pregnancy. Presented cases characterize severe course of AHUS that despite timely diagnostics, early initiation of therapy had an adverse clinical outcome. For the first time in Russian literature described the morphological changes of renal tissue by results of histological studies of autopsy material obtained from patients with AHUS.

Protective effect of hydrogen sulfide on kidneys of type 1 diabetic rats

To explore the protective effects of hydrogen sulfide (H2S) on kidneys of type 1 diabetic rats and its underlying mechanism. Thirty-two male SD rats were randomly divided into four groups:normal control (NC) group, diabetes mellitus (DM) group, DM treatment (NaHS+DM) group and NaHS control (NaHS) group. The rats from DM group and NaHS+DM group were injected intraperitoneally with Streptozotocin 55 mg/kg to induce type 1 diabetes mellitus (n=8). After modeling, rats in NaHS+DM group and NaHS group were intraperitoneally injected with NaHS solution at the dosage of 56 μmol/kg. After 8 weeks, urinary protein content was detected in urine samples collected for 24 h. and the ratio of kidney weight/body weight (renal index) was determined in isolated kidneys. Besides, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured biochemically. The morphological changes of renal tissue were observed by HE staining. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and Caspase-3 in renal tissue were determined by spectrophotometry. The protein expression levels of Bcl-2 and Bax in renal tissue were detected using Western blot. There was no significant difference in the respective measured indexes in rats between NC group and NaHS group. However, in DM group, the levels of 24 h urinary protein, FBG, BUN, Scr and renal index were increased significantly; HE staining showed that the basement membrane was thickened and the amount of glomerular mesangial matrix was increased; MDA content, Caspase-3 activity and Bax expression levels were increased, while SOD activity and Bcl-2 expression were decreased. Compared with those in DM group, the morphological changes of renal tissue and its function were improved; MDA content, Caspase-3 activity and Bax expression were decreased significantly, while SOD activity and Bcl-2 expression were increased obviously in NaHS+DM group. H2S can protect the kidneys of type 1 diabetic rats, which is related to suppressing oxidative stress and cell apoptosis.

Combination of active components of Xiexin decoction ameliorates renal fibrosis through the inhibition of NF-κB and TGF-β1/Smad pathways in db/db diabetic mice.

Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A), Radix et Rhizoma Rhei polysaccharides (P), and Radix Scutellaria flavones (F). Our previous studies have shown that a combination of A, P, and F (APF) exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively) once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB). APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1), and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate that treatment with multi-component herbal therapeutic formulations may be a useful approach for the treatment of diabetic nephropathy.

Активність антиоксидантних ензимів нирок

Salts of heavy metals are excreted by the kidneys and, as pro-oxidants, stimulate the processes of free radical oxidation. Mercury ions are accumulated in the kidneys. So the study of the features of antioxidant enzymes adaptive response of different kidney layers in response to mercury dichloride is important. Catalase and glytathionperoxidase activity within rat kidneys 72 hours after mercury dichloride intoxication in the ratio of 5 ml per 1 kg of the animal weight was studied. It was important to reveal the influence of the mercury salts on rat kidney antioxidative system. Decreasing glytathionperoxidase activity in cortical and cerebral substances and renal papillae were accompanied by increased contents of oxidative modified proteins and lipids and morphological changes in renal tissue under salt and water loading after mercury dichloride poisoning. The results obtained evidence for the inhibition of antioxidative protection of enzymes in rat kidneys under the mercury dichloride effect.

Wound Process in Kidney Parenchyma Following Traditional Partial Nephrectomy Versus Laserassisted Partial Nephrectomy in Experiment

The purpose of the study To compare the morphological changes in renal tissue following traditional partial nephrectomy versus laserassisted partial nephrectomy. Material and methods 100 mature male Wistar rats were included in experiment. A diode laser-emitting light at a wavelength of 970 nm of ЛСП «ИРЭ-Полюс» model ЛСП 0,97/10 laser was used for partial nephrectomy. General conditions of animals and morphological changes in renal tissue following traditional partial nephrectomy with warm ischaemia and laserassisted partial nephrectomy were evaluated during the experiment. Results and their discussion the reparation of kidney parenchyma in a resection margin was more fluent after laserassisted partial nephrectomy with the laser-emitting light at a wavelength of 970 nm in continuous-wave mode. Also there were not any morphological changes in renal tissue following laserassisted partial nephrectomy. Conclusion the comparative analysis showed that the diode laser-emitting light at a wavelength of 970 nm is promising method for using in clinical practice

Renal Alterations in Feline Immunodeficiency Virus (FIV)-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

Protective effects of glycyrrhizin on adriamycin nephropathy in rats

To observe the effects of glycyrrhizin on laminin (LN) expression in kidney tissue and excretory quantity of urine protein of rats with adriamycin nephropathy, and to explore the protective effects of glycyrrhizin on glomerulosclerosis. Eighteen SD rats were randomly divided into 3 groups: normal control group (n=6), untreated group (n=6) and glycyrrhizin-treated group (n=6). Adriamycin nephropathy was induced in rats in the last two groups by intravenous injection of adriamycin. The rats in the glycyrrhizin-treated group were fed glycyrrhizin for eight weeks, whereas the rats in the normal control group and untreated group were fed normal saline solution for eight weeks too. The levels of 24 h urine protein (Upr), serum creatinine (sCr), blood urea nitrogen (BUN) and serum cholesterol (Ch) of rats in each group were examined before treatment and after the treatment for four and eight weeks. The renal morphological changes were observed under a microscope. The expression level of LN in renal tissue was detected by streptavidin-biotin peroxidase complex (SABC) method. The levels of 24 h Upr after the treatment for four and eight weeks in the glycyrrhizin-treated group were both significantly decreased as compared with those in the untreated group. The pathological morphological changes of renal tissue in the glycyrrhizin-treated group were remarkably alleviated, and the expression level of LN in renal tissue was also decreased in the glycyrrhizin-treated group as compared with those in the untreated group. The glycyrrhizin exerts certain protective effects on adriamycin nephropathy in rats by reducing excretory quantity of urine protein, decreasing expression level of LN in renal tissue, improving renal function and lessening the severity degree of glomerulosclerosis so as to retard the development of glomerulosclerosis.

Streptococcal IgG Fc-binding proteins are factors initiating experimental glomerulonephritis

Immunomorphological analysis of renal tissue from rabbits immunized with group A streptococci differing in the expression of IgG Fc-binding proteins showed that only IgG Fc-positive streptococci induced destructive degenerative changes in the kidneys classified as membranous proliferative glomerulonephritis with symptoms of fibroplastic glomerulonephritis. These morphological changes in renal tissue are comparable to changes in patients with acute poststreptococcal glomerulonephritis. Depositions of IgG and C3 complement component on the basal membrane of renal glomeruli and secretion of antiinflammatory cytokines IL-1s, IL-6, and TNF-α by mesangial cells were revealed. No destructive changes were found in the kidneys of rabbits immunized with IgG Fc-negative streptococcus strain or isogenic mutant completely devoid of genes responsible for the expression of IgG Fc-binding proteins. Thus streptococcal IgG Fc-binding proteins determine the development of experimental glomerulonephritis in rabbits.