Pathological Changes Of Liver Tissues Research Articles

Modified synthetic siRNA targeting tissue inhibitor of metalloproteinase‐2 inhibits hepatic fibrogenesis in rats

Fibrosis occurs in most chronic liver injuries and results from changes in the balance between synthesis and degradation of extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are known to regulate the ECM turnover. We investigate the effect of modified synthetic small interfering RNA (siRNA) targeting TIMP-2 in rat model of liver fibrosis. Rat hepatic fibrosis was induced by CCl4 for 8 weeks. After the 2-week CCl4 injection period, rats in the three siRNA groups simultaneously received a different dosage (0.05, 0.1 and 0.2 mg.kg(-1), respectively) of modified synthetic siRNA targeting TIMP-2 via the tail vein every 3 days for 6 weeks. The pathological changes in liver tissues were observed by light microscopy and transmission electron microscopy. Portal vein pressure and proliferating cell nuclear antigen were measured. Expression of TIMP-2, MMP-2, MT1-MMP, MMP-13, hepatocyte growth factor, collagen type I, collagen type III and alpha-SMA were evaluated by quantitative real-time polymerase chain reaction or Western blotting or gelatin zymography. Modified synthetic siRNA targeting TIMP-2 induced a dose-dependent inhibition of the TIMP-2 expression in the rat model of liver fibrosis with a similar trend in MMP-2 and MT1-MMP, but an increase in MMP-13. Rats administered siRNA targeting TIMP-2 showed promotion of ECM degradation, reduction in activated hepatic stellate cells and enhancement of hepatocyte regeneration. Furthermore, portal hypertension was also ameliorated after treatment with siRNA targeting TIMP-2. Knock-down of TIMP-2 expression attenuates CCl4-induced liver fibrosis and is a potential pharmacological target for gene therapy in liver fibrosis.

Effect of pectin and amidated pectin on cholesterol homeostasis and cecal metabolism in rats fed a high-cholesterol diet

Two experiments were performed to compare the effect of pectin and its hydrophobic derivatives on homeostasis of cholesterol and cecal metabolism in male young rats. Control rats were fed a diet supplemented with palm fat and cholesterol (50 and 10 g/kg, respectively). Rats of other groups were fed the same diet containing citrus pectin or octadecylpectinamide (60 g/kg). Diets were fed for 4 weeks. In experiment I, pectinamide of lower degree of amidation (30 %) increased serum HDL cholesterol from 1.20 to 1.43 micromol/ml (p>0.05) at the expense of other cholesterol fractions. In experiment II, pectinamide of a higher degree of amidation (53 %) significantly decreased total serum cholesterol from 2.08 to 1.67 micromol/ml. Amidated pectins at both levels of substitution significantly decreased hepatic concentrations of cholesterol and fat. In both experiments the relative weight of cecum in the pectinamide group was significantly lower than in pectin group. The highest cecal concentrations of short-chain fatty acids (SCFA) were found in rats fed a diet with pectin (133.2 and 129.3 micromol/g in experiment I and II, respectively). In other groups, cecal SCFA was significantly (pectinamide groups) or non-significantly (controls) lower. In wet feces, SCFA concentrations were higher and butyrate molar proportions lower than in corresponding cecal contents. Pectinamide of a lower or higher degree of substitution significantly increased fecal content of cholesterol from 18.5 and 17.3 micromol/g in controls to 31.8 and 28.0 micromol/g, respectively. Corresponding concentrations of coprostanol were decreased. Effects of pectin on cholesterol homeostasis were absent or marginal. Histological examination revealed that hepatic tissue of control and pectin-fed rats was infiltrated with lipids. The Sudan black-positive material was absent in the liver of rats fed pectinamides. No pathological changes of liver tissue were apparent. In summary, hydrophobic amidated pectins significantly altered cholesterol homeostasis in rats and might be considered as a clinically effective hypocholesterolemic agent. Low cecal SCFA concentrations in rats fed pectinamides suggest that amidation of pectin had decreased its fermentability.

Effects of Huatan Xiezhuo Recipe on insulin resistance and leptin in rats with fatty liver

To observe the effects of Huatan Xiezhuo Recipe (HTXZR) on fatty liver of rats. Forty-eight SD rats were randomly divided into five groups: normal control group, untreated group, Dongbao Gantai Tablet (DBGTT)-treated group, low-dose HTXZR-treated group and high-dose HTXZR-treated group. Fatty liver was induced in the rats by hyperlipid diet and intraperitoneal injection of tetracycline. The pathological changes of liver tissues in rats were observed, and the liver function, serum leptin, insulin resistance index, triglyceride (TG) and free fatty acid (FFA) in the liver were detected. The levels of serum leptin, insulin resistance index, FFA and TG in rats of the three treated groups were lower than those of the untreated group (P<0.01), and such effects in the HTXZR-treated groups were more significant than those in the DBGTT-treated group (P<0.05). The main action mechanisms of HTXZR in treating fatty liver are probably to promote the lipid metabolism, decrease the leptin and insulin resistance.

Histopathological changes after microwave coagulation therapy for patients with hepatocellular carcinoma: review of 15 explanted livers

Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT observed in explanted livers in relation to CT findings. A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Explanted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections. Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. Histologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas. Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body-like inflammatory reaction and fibrosis. Pathologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed.

Histopathological changes after microwave coagulation therapy for patients with hepatocellular carcinoma: review of 15 explanted livers

Objectives Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT observed in explanted livers in relation to CT findings. Methods A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Explanted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections. Results Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. Histologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas. Conclusions Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body–like inflammatory reaction and fibrosis. Pathologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed.

Synthesis of endotoxin receptor CD14 protein in Kupffer cells and its role in alcohol-induced liver disease.

To observe the synthesis of endotoxin receptor CD14 protein and its mRNA expression in Kupffer cells (KCs), and evaluate the role of CD14 in the pathogenesis of liver injury in rats with alcohol-induced liver disease (ALD). Twenty-eight Wistar rats were divided into two groups: ethanol-fed group and control group. Ethanol-fed group was fed ethanol (dose of 5g-12 g/kg/d) and control group received dextrose instead of ethanol. Two groups were sacrificed at 4 wk and 8 wk, respectively. KCs were isolated and the synthesis of CD14 protein and its mRNA expression in KCs were determined by flow cytometric analysis (FCM) or the reverse transcription polymerase chain reaction (RT-PCR) analysis. The levels of plasma endotoxin and alanine transaminase (ALT) were measured by Limulus Amebocyte Lysate assay and standard enzymatic procedures respectively, and the levels of plasma tumor necosis factor (TNF)-alpha and interleukin (IL)-6 were both determined by ELISA. The liver pathology change was observed under light and electric microscopy. In ethanol-fed group, the percentages of FITC-CD14 positive cells were 76.23 % and 89.42 % at 4 wk and 8 wk, respectively. Compared with control group (4.45 % and 5.38 %), the difference was significant (P<0.05). The expressions of CD14 mRNA were 7.56+/-1.02 and 8.74+/-1.37 at 4 wk and 8 wk, respectively, which were significantly higher compared with the control group (1.77+/-0.21 and 1.98+/-0.23) (P<0.05). Plasma endotoxin levels at 4 wk and 8 wk increased significantly in ethanol-fed group (129+/-21 ng/L and 187+/-35 ng/L) than those in control rats (48+/-9 ng/L and 53+/-11 ng/L)(P<0.05). Mean values of plasma ALT levels increased dramatically in ethanol-fed rats (112+/-15 IU/L and 147+/-22 IU/L) than those in the control animals (31+/-12 IU/L and 33+/-9 IU/L) (P<0.05). In ethanol-fed rats, the levels of TNF-alpha were 326+/-42 ng/L and 402+/-51 ng/L at 4 wk and 8 wk, respectively which were significantly higher than those in control group (86+/-12 ng/L and 97+/-13 ng/L) (P<0.05). The levels of IL-6 were 387+/-46 ng/L and 413+/-51 ng/L, which were also higher than control group (78+/-11 ng/Land 73+/-10 ng/L) (P<0.05). In liver section from ethanol-fed rats, there were marked pathological changes including steatosis, cell infiltration and necrosis. No marked pathological changes were seen in control group. Ethanol administration led to a significant synthesis of endotoxin receptor CD14 protein and its gene expression in KCs, which maybe result in the pathological changes of liver tissue and hepatic functional damages.

Morphometric investigations on the portal tracts of the liver, the differentiation of variable progression in chronic persistent hepatitis.

Morphometric investigations were carried out on the portal tracts of the liver in different forms of chronic hepatitis. The investigation groups each contained 25 liver biopsies, which were subdivided into cases with normal liver, a subsiding acute virus hepatitis, three different forms of chronic persistent hepatitis (CPH) and chronic aggressive hepatitis type IIa (CAH IIa). Determinations of the volume and surface of the portal tracts and their components enabled three forms of COH (type Ia, Ib, Ic) to be characterised. Preliminary clinical and semiquantitative histological investigations were correlated with a significant difference in the histological characteristics and prognosis. HBsAg-positive and HBsAg-negative cases showed no significant morphologically detectable differences in all grups investigated. Morphometry is suitable for investigation of pathological changes in liver tissue, especially the portal tracts.

The Relation of Pathological Changes of Liver Tissue to Electrophoretic Findings in Serum from Horses affected with Equine Infections Anemia

The relationships between the histopathological changes of liver and the electrophoretic findings (a decrease of albumin and an increase of γ-globulin) in serum protein were investigated on liver tissue and sera which had been obtained from 36 horses affected with equine infectious anemia.It was found that the strength of histopathological changes of liver tissue was closely connected with both the decrease of albumin and the increase of γ-globulin. Especially, the findings of swelling and increase of reticulo-endotherial-system (RES) and appearance of histiocytes in the sinusoid of hepatic lobulus showed clear relation to the decrease of albumin and the increase of γ-globulin. The degree of infiltration of lymphoid cells showed also some relation to the increase of γ-globulin. It should be considered that the decrerse of albumin appeared secondarily to the increase of γ-globulin. It could be presumed, therefore that the increase of activity of RES caused that of γ-globulin. This thought is different from that of lymphocyte-theory and plasma-cell-theory. It is possible, however, to presume that the antibody-globulin may be produced by lymphocytes or plasma cells, and that the abnormal γ-globulin may be produced by activated RES.