Macleaya cordata isoquinoline alkaloids attenuate Escherichia coli lipopolysaccharide-induced intestinal epithelium injury in broiler chickens by co-regulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways.

Effect of berberine on LPS-induced intestinal epithelial injury and m6A methylation in broilers.

To date, mechanisms of sepsis-induced intestinal epithelial injury are not well known. P2X7 receptor (P2X7R) regulates pyroptosis of lymphocytes, and propofol is usually used for sedation in septic patients. We aimed to determine the occurrence of enterocyte pyroptosis mediated by P2X7R and to explore the effects of propofol on pyroptosis and intestinal epithelial injury after lipopolysaccharide (LPS) challenge. A novel regimen of LPS challenge was applied in vitro and in vivo. Inhibitors of P2X7R (A438079) and NLRP3 inflammasome (MCC950), and different doses of propofol were administered. The caspase-1 expression, caspase-3 expression, caspase-11 expression, P2X7R expression and NLRP3 expression, extracellular ATP concentration and YO-PRO-1 uptake, and cytotoxicity and HMGB1 concentration were detected to evaluate enterocyte pyroptosis in cultured cells and intestinal epithelial tissues. Chiu's score, diamine oxidase and villus length were used to evaluate intestinal epithelial injury. Moreover, survival analysis was performed. LPS challenge activated caspase-11 expression and P2X7R expression, enhanced ATP concentration and YO-PRO-1 uptake, and led to increased cytotoxicity and HMGB1 concentration. Subsequently, LPS resulted in intestinal epithelial damage, as evidenced by increased levels of Chiu's score and diamine oxidase, and shorter villus length and high mortality of animals. A438079, but not MCC950, significantly relieved LPS-induced enterocyte pyroptosis and intestinal epithelial injury. Importantly, propofol did not confer the protective effects on enterocyte pyroptosis and intestinal epithelia although it markedly decreased P2X7R expression. LPS attack leads to activation of caspase-11/P2X7R and pyroptosis of enterocytes. Propofol does not reduce LPS-induced pyroptosis and intestinal epithelial injury, although it inhibits P2X7R upregulation.

Simple SummaryIn intensive farms, broilers are easily infected by harmful bacteria, resulting in intestinal damage and affecting their health. The prohibition of antibiotics makes it necessary to find new antibacterial products, especially native substances. As a kind of traditional Chinese herbal medicine, Chinese gallotannins (CGT) containing tannins have antioxidant, anti-inflammatory, and bactericidal effects. Therefore, in this experiment, we established a model of intestinal injury in broilers by intraperitoneal administration of lipopolysaccharide (LPS) in Escherichia coli to explore the protective effect of CGT on intestinal injury in broilers induced by LPS challenge. The results show that CGT effectively alleviated intestinal mucosal injury and repaired the intestinal barrier effectively by repairing intestinal villus morphology, inhibiting apoptosis, decreasing pro-inflammatory factors, and stabilizing microbial ecology, thus raising the body weight to a normal level. A dietary supplementation of 300 mg/kg CGT might be a potential way to substitute antibiotics to attenuate intestinal injury induced by LPS in broilers.This experiment was conducted to study the protective effects of dietary Chinese gallotannins (CGT) supplementation against Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury in broilers. Four hundred and fifty healthy Arbor Acres broilers (one-day-old) were randomly divided into three groups: (1) basal diet (CON group), (2) basal diet with LPS challenge (LPS group), and (3) basal diet supplemented with 300 mg/kg CGT as well as LPS challenge (LPS+CGT group). The experiment lasted for 21 days. Intraperitoneal LPS injections were administered to broilers in the LPS group and the LPS+CGT group on days 17, 19, and 21 of the trial, whereas the CON group received an intraperitoneal injection of 0.9% physiological saline. Blood and intestinal mucosa samples were collected 3 h after the LPS challenge. The results showed that LPS administration induced intestinal inflammation and apoptosis and damaged small intestinal morphology and structure in broilers. However, dietary supplementation with CGT alleviated the deleterious effects on intestinal morphology and barrier integrity caused by the LPS challenge, while also reducing intestinal apoptosis and inflammation, enhancing intestinal antioxidant capacity, and increasing cecal microbial alpha diversity in the LPS-challenged broilers. Therefore, our findings demonstrated that a 300 mg/kg CGT addition could improve intestinal morphology and gut barrier structure, as well as maintaining bacterial homeostasis, in broilers exposed to LPS. This might partially be attributed to the reduced cell apoptosis, decreased inflammatory response, and enhanced antioxidant capacity in the small intestinal mucosa.

Objective To investigate the protective mechanisms of ulinastatin (UTI) and dexamethasone (DXM) against acute lung injury (ALI) induced by lipopolysaccharide (LPS) endotoxin in rats.Methods Twenty four male Sprague-Dawley rats were randomly divided into four groups with 6 mice each group:control group (Con group),LPS group,LPS plus ulinastatin group (UTI group),LPS plus dexamethasone group (DXM group).Rats were killed at 8 h time points,and the protein and mRNA expression levels of glucocorticoid receptor (GR) in the lungs were detected by Western blot and Real Time fluorescent quantitative PCR.The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 were also tested by enzyme linked immunosorbent assay (ELISA) and at the same time we tested the lung wet/dry weight radio(W/D).The pathological changes in lung tissue were evaluated by HE staining.Results ① The protein expression levels of GR:LPS group (0.418±0.018) was significantly lower than that in control group (0.841±0.021)(P＜0.05).The protein expression levels of GR in UTI group (0.692±0.018) and DXM group (0.702± 0.024)were higher than that in LPS group (P＜0.05).No significant differences were found between UTI and DXM group in the protein expression levels of GR (P＞0.05).② The expression levels of GRmRNA:LPS group was significantly lower,but the expression level of GRmRNA in UTI group was slightly higher than that in LPS group.No significant differences were found between UTI and LPS group in the expression levels of GRmRNA (P＞0.05),but the expression level of GRmRNA in DXM group was significantly higher than that in UTI group,LPS group and Con group(P＜0.05).③ The expression level of TNF-α:LPS group(374±8) ng/L was significantly higher than that in control group (102±6) ng/L(P＜0.05),the expression level of TNF-α in UTI group(343± 6) ng/L and DXM group(282±8) ng/L fell in between control group and LPS group,but the expression level of TNF-α in DXM group were lower than that in UTI group and higher than those in LPS group,Con group (P＜0.05).④ The expression levels of IL-10:LPS group (264±10) ng/L was significantly higher than that in control group (43±3) ng/L (P＜0.05).In UTI group (369±10) ng/L,the expression level of IL-10 was higher than that in LPS group(P＜0.05).The expression level of IL-10 in DXM group (180±7) ng/L fell in between control group and LPS group (P＜0.05).⑤ The lung W/D:LPS group (5.58±0.28) was significantly higher than that in control group(4.33±0.27)(P＜0.05),the lung W/D in UTI group (5.15±0.18) and DXM group (4.79±0.21) fell in between control group and LPS group (P＜0.05),but the lung W/D in DXM group were lower than that in UTI group (P＜0.05).⑥ Histopathologic examination of lungs:destroyed lung structure,inflammatory cells infiltration,widened alveolar septum with bleeding and edema were seen in LPS group.However,pathological changes in UTI group were milder than those in LPS group and pathological changes in group DXM milder than those in UTI group.Conclusions The protective mechanisms of UTI and DXM against ALI induced by LPS endotoxin in rats are not the same.The protective effect of DXM against ALI is better than UTI. Key words: Acute lung injury; Glucocorticoid receptor; Lipopolysaccharide; Ulinastatin; Dexamethasone

Objective To investigate the protective effects and mechanism of insulin(INS) on brain in septic rats, and explore the possible role of uncoupling protein 2 (UCP2) in these effects. Methods Fifty male specific pathogen free(SPF) Sprague-Dawley rats were randomly divided into normal control (CN) group(n=10), lipopolysaccharide(LPS) group(n=20) and INS group (n=20) according to random number table.The septic rat model was established through an intraperitoneal injection of 15 mg/kg LPS of gram- negative bacteria.The rats in the INS group received a 1 U/kg INS injection subcutaneously 30 minutes before the injection of LPS, and the rats in the CN group were given equivalent 9 g/L saline in the same way.Eight rats in each group were killed, and their cerebral cortex were collected after the injection of LPS for 24 h. Pathological change of cerebral cortex was detected by Hematoxylin-Eosin(HE) staining.The cerebral cortex mitochondia were extracted for detecting the levels of reactive oxygen species(ROS), malondialdehyde (MDA) and the activity of superoxide dismutase(SOD). Neuronal apoptosis was detected by terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining.UCP2 mRNA expression was detected by quantitative real-time(RT)-PCR.Apoptosis-associated protein B lymphocyte tumor-2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved cysteinyl aspartate specific protease(cleaved Caspase-9) and UCP2 protein expression were determined by Western blot. Results (1)Compared with the CN group, obvious abnormal pathological change was revealed by HE staining in cerebral cortex of rats in the LPS group and the INS group, but the pathological change was attenuated in the INS group compared with the LPS group.(2)Compared with the CN group, the levels of mitochondrial ROS[(210.01±14.09) RFU vs.(49.06±7.28) RFU] and MDA[(2.19±0.18) nmol/mg pro vs.(1.25±0.11)nmol/mg pro]in the LPS group significantly increased, whereas SOD activity significantly decreased [(238.49±35.60) U/g pro vs.(446.66±24.90)U/g pro], and the differences were significant(all P<0.05). Compared with the LPS group, the levels of ROS [(152.69±15.83) RFU vs.(210.01±14.09) RFU] and MDA[(1.55±0.14) nmol/mg pro vs.(2.19±0.18) nmol/mg pro] in the INS group decreased, while SOD activity increased[(327.8±23.26) U/g pro vs.(238.49± 35.60) U/g pro], and the differences were significant(all P<0.05). (3)Compared with the CN group, the neuronal apoptosis index of cortex in the LPS group was elevated[(54.16±6.84)% vs.(5.45±1.43)%], while the expression of Bcl-2 decreased (627±0.018 vs.0.739±0.020), but the expressions of Bax(0.768±0.019 vs.0.520±0.010) and cleaved Caspase-9(0.739±0.016 vs.0.467±0.030) increased, and the differences were significant(all P<0.05). Compared with the LPS group, the neuronal apoptosis index of cortex in the INS group decreased [(33.30±3.07)% vs.(54.16±6.84)%], but the Bcl-2 expression increased (0.743±0.022 vs.0.627±0.018), and Bax (0.687±0.034 vs.0.768±0.019) and cleaved Caspase-9(0.551±0.013 vs.0.739±0.016) were reduced, and the differences were significant (all P<0.05). (4)Compared with the CN group, the mRNA (2.248±0.155 vs.1.000±0.100) and protein expression of UCP2 (0.659±0.016 vs.0.599±0.018) were elevated in the LPS group.Compared with the LPS group, the UCP2 mRNA (2.944±0.117 vs.2.248±0.155) and UCP2 protein (0.719±0.018 vs.0.659±0.016) increased, and the differences were significant(all P<0.05). Conclusions INS can protect the brain of septic rats through alleviating mitochondrial oxidative stress and inhibiting the mitochondrial-initiated apoptotic pathway to reduce neuronal apoptosis.INS upregulates UCP2 expression in the brain of septic rats, which may play a role in the protective effects mentioned above. Key words: Sepsis; Brain; Insulin; Reactive oxygen species; Oxidative stress; Apoptosis; Uncoupling protein 2

To explore the effects of lipoxin A(4) (LXA(4)) on lipopolysaccharide (LPS)-induced oxidative stress in human umbilical veins endothelial cells (HUVEC) and the possible mechanism. Neonatal umbilical cords were obtained from normal term pregnant women with cesarean section within 4 hours and then were used to isolate HUVEC for subculture. HUVEC were divided into four groups:control group; LPS group (10 µg/ml of LPS); LPS + LXA(4) group (10 µg/ml of LPS and 100 nmol/L of LXA(4)); LXA(4) group (100 nmol/L of LXA(4)). All expriments were performed after cells treated for 12 and 24 hours respectively. Immunofluorescence was used to detect the expression of VIII foctor and nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2); the mRNA expression of Nrf2, heme oxygenase 1 (HO-1) and reduced form of nicotinamide-adenine dinucleotide quinone oxidoreductase-1 (NQO1) were evaluated by reverse transcription-PCR. (1) The flavovirens fluorescence was observed in the cytoplasm under fluorescence microscope, which confirmed the existence of VIII factor which specifically expressed in endothelial cells, especially in HUVEC. (2) Immunofluorescent results showed that in control group, Nrf2 protein expressed in the cytosol rather than in the nucleus. In LPS group, the expression of Nrf2 protein obviously increased in the nucleus while decreased in the cytosol after 12 hours. However, after LPS treatment for 24 hours, Nrf2 expression reduced in the cytosol and nucleus. In co-treatment with LPS and LXA(4) group, the expression of Nrf2 protein was much higher than that in LPS group after 12 hours or 24 hours. Furthermore, Nrf2 protein also mostly expressed in the cytosol in LXA(4) group. (3) After stimulation for 12 hours, compared with control group, the gene expression of Nrf2 and HO-1 were significantly enhanced in LPS group (0.581 ± 0.019 and 0.081 ± 0.009, P < 0.05) and in LPS + LXA(4) group (0.692 ± 0.048 and 0.136 ± 0.018, P < 0.05), the level of NQO1 mRNA in LPS group and LPS + LXA(4) group were 0.381 ± 0.009 (P > 0.05) and 0.574 ± 0.034 (P < 0.05). After treatment for 24 hours, compared with control goup, the gene expressions of Nrf2 and NQO1 were down-regulated in LPS group (0.180 ± 0.017 and 0.472 ± 0.064, P < 0.05). But in LPS + LXA(4) group the expression of Nrf2 and NQO1 were upregulated (0.532 ± 0.051 and 0.830 ± 0.068, P < 0.05, compared with treatment for LPS group). The mRNA expressions of Nrf2, HO-1 and NQO1 were increased in LPS + LXA(4) group compared with LPS group (P < 0.05). In addition, there was no markedly difference in the expressions of Nrf2, HO-1 and NQO1 between control and LXA(4) group after 12 hours and 24 hours (P > 0.05). Through activating nuclear translocation of Nrf2 protein from cytoplasm, LXA(4) upregulates the Nrf2 downstream enzymes, such as NQO1 and HO-1 to protect HUVEC against the oxidative stress induced by LPS.

Trans-anethole ameliorates LPS-induced inflammation via suppression of TLR4/NF-κB pathway in IEC-6 cells

"CHOP"ing intestinal stem cells on way to cholestatic liver injury.

The study was performed to see the effects of coenzyme Q10 (CoQ10) on blood biochemical components and hepatic antioxidant system in rats exposed to lipopolysaccharide (LPS)-induced toxicity. A total of 24 rats were allocated to four groups: control (CON), 100 mg/kg BW of LPS (LPS), 100 mg of CoQ10/kg BW with LPS (LCQI) and 300 mg of CoQ10/kg BW with LPS (LCQII). The LPS and LCQI groups showed a significant (P<0.05) increase in the relative spleen weight compared with the CON group without affecting body and liver weights. The blood alanine aminotransferase (ALT) level in the LPS group was significantly (P<0.05) greater than that in the CON group, while supplementation with 100 or 300 mg CoQ10 to rats injected with LPS normalized the ALT level in the CON group. In antioxidant systems, the LPS group showed a significantly (P<0.05) higher mRNA and activity of superoxide dismutase (SOD) than the CON group. The supplementation with CoQ10 to the LPS-treated group normalized the level of SOD, which was comparable to the level of the CON group. Both the mRNA expression and activity of glutathione peroxidase in the LCQI and LCQII groups were higher (P<0.05) than that of the LPS group. However, administration of LPS or CoQ10 unaffected the level of catalase and total antioxidant power. The level of lipid peroxidation in the LCQII group was lower (P<0.05) than that in the LPS group. In conclusion, CoQ10 exerted its favorable effect against liver damage by modulation of antioxidant enzymes in LPS treated rats.

Objective To investigate the role of glucocorticoid-induced tumor necrosis factor ligand (GITRL) in regulating the inflammatory reaction of kupffer cells.Methods The kupffer cells and T cells of mice were isolated and divided into 6 groups after being co-cultured:control group,kupffer cells and T cells were cultured in DMEM only; lipopolysaccharide (LPS) group,kupffer cells and T cells were cultured in media with LPS (1 mg/L) ; LPS + GITRL siRNA group,kupffer cells and T cells were cultured in media as the LPS group after transfected with GITRL siRNA ; LPS + control siRNA group,kupffer cells and T cells were cultured in media as the LPS group after transfected with control siRNA; LPS + pEGFP-N1 GITRL group,kupffer cells and T cells were cultured in media as the LPS group after transfected with pEGFP-N1 GITRL plasmid; LPS + pEGFP-N1 control group,kupffer cells and T cells were cultured in media as the LPS group after transfected with control plasmid.After 24 hours of treatment,the expressions of GITRL and PDL1 of kupffer cells were detected by immunofluorescence and western blot,respectively.The proliferation and apoptosis of T cells were measured by MTF assay and Annexin V/PI flow cytometry,respectively.The expression of tumor necrosis factor (TNF-α) in the supernatant fluid was measured by ELISA.All data were analyzed using the independent t test and one-way analysis of variance.Results The transfection efficiencies of GITRL siRNA and pEGFP-N1 GITRL were 90％ and 85％,respectively.Compared with normal kupffer cells,the protein expression of GITRL of kupffer cells transfected with GITRL siRNA was significantly decreased,while the protein expression of GITRL of kupffer cells transfected with pEGFP-N1 GITRL was significantly increased (t =41.72,13.10,P ＜ 0.05).There was no significant difference in the protein expressions of GITRL between normal kupffer cells and those in the control groups (F =2.27,P ＞ 0.05).The fluorescence intensity of GITRL in the LPS group was significantly higher than that in the control group (t =49.29,P ＜ 0.05).Compared with LPS group,the activation of GITRL expression by the LPS was significantly suppressed in the LPS + GITRL siRNA group (t =9.84,P ＜ 0.05),while the expression of GITRL in the LPS + pEGFP-N1 GITRL group was significantly increased (t =5.78,P ＜ 0.05).There was no significant difference in the GITRL expression among the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =0.86,P ＞ 0.05).The expression of PDL1 in the LPS group was significantly lower than that in the control group (t =18.83,P ＜0.05).Compared with LPS group,the expression of PDL1 in the LPS + pEGFP-N1 GITRL group was significantly suppressed (t =11.79,P ＜ 0.05),while the expression of PDL1 in the LPS + GITRL siRNA group was significantly stronger (t =19.08,P ＜ 0.05).There was no significantly difference in the expression of PDL1 in the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =2.22,P ＞ 0.05).The proliferation of T cells was increased and the number of apoptotic T cell was decreased in the LPS group when compared with control group (t =49.43,40.11,P ＜ 0.05).Compared with LPS group,the proliferation and apoptosis of T cells in the LPS + pEGFP-N1 GITRL group had the same trend (t =5.77,12.64,P ＜0.05); while the proliferation of T cells was decreased and the apoptosis of T cells was increased in the LPS + GITRL siRNA group (t =17.00,49.90,P ＜ 0.05).There was no significant difference in the proliferation and apoptosis of T cells among the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =1.87,1.35,P ＞ 0.05).The expression of TNF-α was significantly higher in the LPS group than that in the control group (t =125.68,P ＜ 0.05).Compared with the LPS group,the expression of TNF-α was significantly decreased in the LPS + GITRL siRNA group (t =119.65,P ＜ 0.05),while the expression of TNF-α in the LPS + pEGFP-N1 GITRL group was significantly increased (t =147.70,P ＜ 0.05).There was no significant difference in the TNF-α expression among the LPS + control siRNA group,LPS + pEGFP-N1 control group and LPS group (F =0.14,P ＞ 0.05).Conclusion Kupffer cells suppress the expression of PDL1 by upregulating GITRL,and thus activate the proliferation of T cells and promote the inflammatory reaction.The immunologic balance may be recovered after the interference of GITRL to restrain the inflammatory reaction. Key words: Sepsis; Glucocorticoid-induced tumor necrosis factor receptor ligand; Programmed death ligand ; Kupffer cells ; T cells

Objective To detect the effect of penhyclidine hydrochloride (PHC) on blood-brain barrier permeability in rats with lipopolysaccharide (LPS)-induced brain injury. Methods Eighty-one clear adult male SD rats were divided into control group, LPS group and PHC group according to the random number table, with 27 rats per group. The model of LPS-induced brain injury was established both in LPS and PHC groups. Rats were treated intraperitoneally with 2 mg/kg PHC in PHC group, while with the same volume of normal saline in control and LPS groups. Evans blue propagation through the brain was detected under the fluorescence microscope. Evans blue content was measured with a spectrophotometer. TNF-α content was measured with the Elisa assay. Brain water content was assessed with wet-to-dry weight ratios. Results Evans blue distribution in the cortex was obvious in LPS group, but decreased in PHC group. In control group contents of Evans blue in the cortex [(10.2±1.4)μg/g] and in the hippocampus[(11.3±0.8)μg/g] lowered as compared to these in LPS group [(234.8±14.7) and (23.1±1.9)μg/g] and PHC group [(71.0±8.7) and (15.2±1.9)μg/g] (P<0.01). Brain water content in control group was (73.5±1.8)%, increased to (85.3±1.6)% in LPS group and (78.9±1.2)% in PHC group (P<0.01). In control group contents of TNF-α in blood serum [(40.6±4.4) pg/ml], cerebrospinal fluid [(84.0±8.6)pg/ml] and brain tissue [(156.3±11.8) pg/ml] were significantly lower than these in LPS group[(93.4±7.2), (176.4±11.6) and (280.8±19.4)pg/ml] and PHC group[(79.9±5.9), (146.2±7.4) and (216.9±14.5) pg/ml] (P<0.01). And in comparison, all the measurements were lower in PHC group than in LPS group (P<0.01). Conclusion PHC can protect the BBB in rats with LPS-induced brain injury. Key words: Brain injuries; Blood-brain barrier; Penhyclidine hydrochloride

Objective To study the protective role of pre-resolving mediator lipoxin A4(LXA4) in the NA+ -K+-ATPase in alveolar type Ⅱ (AT Ⅱ ) epithelial cells of rats exposed to lipopolysaccharide (LPS). Method The AT Ⅱ cells were isolated and purified, and divided randomly into control group (PBS), vehiculum (alcohol 0.7 μL/mL) group, LPS (1 μg/mL) group, LXA4(1/10 mol/mL) group and LPS (1 μg/mL LPS) + LXA4(1/10 mol/mL) group. After exposure to LPS and/or LXA4 for4 hours, NA+-K+ -ATPase and β1-subunits mRNA in AT Ⅱ epithelial cells were detected by using RT-PCR, and ATP, ADP, AMP, total adenine nucleotides (TAN) and energy charge (EC) were measured by using high performance liquid chromatography (HPLC), and then the activities of Na+-K+-ATPase were calculated accordingly. Results The NA+-K+-ATPase α-subunit and β-subunit mRNA were significantly decreased in LPS group ( P ＜ 0.05 vs. control group). However, the expressions of NA+ -K+-ATPase mRNA were significantly enhanced by application of LXA4 to AT Ⅱ epithelial cells exposed to LPS (P ＜0.05 vs. LPS group). The activities of NA+ -K+ -ATPase were enhanced in LPS group (P ＜0.05 vs. control group). Compared with control group and LPS group, the activities of NA+-K+-ATpase in LPS + LXA4 group were significantly increased (P ＜0.01 vs. control group; P ＜0.05 vs. LPS group). The EC of AT Ⅱ epithelial cells were higher in LPS group ( P ＜ 0.01 vs. control group). There were no significant differences in EC between control group and LPS + LXA4group(P ＞0.05). Conclusions The pro-resolving mediator LXA4 can enhance the expressions of NA + -K + -ATPase α-subunit and β-subunit mRNA, and the activities of NA + -K + -ATPase in AT Ⅱ epithelial cells or rats exposed to LPS, and ca also balance the metabolism of AT Ⅱ epithelial cells. These findings suggest that LXA4 plays an important role in lung edema clearance in lung injury induced by endotoxin, and the role is likely associated with the enhancement of the expressions of Na+ -K+ -AT-Pase α-subunit and β-subunit, and the activities of Na+ -K* -ATPase, maintaining the balance of metabolism of AT Ⅱ epithelial cells. Key words: Lipoxin A4 (LXA4); Na+-K+-ATPase; Alveolar type Ⅱ epithelial cells(AT Ⅱ ); Lipopolysaccharide (LPS)

Dietary α-Ketoglutarate Alleviates Escherichia coli LPS-Induced Intestinal Barrier Injury by Modulating the Endoplasmic Reticulum-Mitochondrial System Pathway in Piglets

Simple SummaryThe biological characteristics of E. faecium R1 and the effect of dietary supplementation with E. faecium R1 on the growth performance of weaned piglets were studied. The results showed that E. faecium R1 had the characteristics of effective bacteriostatic activity, acid resistance, bile salt resistance, and high-temperature resistance. Dietary supplementation with E. faecium R1 (6.5 × 106 CFU/g) improved intestinal function of weaning piglets by decreasing diarrhea incidence. Further research found that dietary supplementation with E. faecium R1 (6.5 × 106 CFU/g) attenuated intestinal and liver injury in piglets challenged by lipopolysaccharide.In this study, a strain of E. faecium R1 with effective bacteriostatic activity, acid resistance, bile salt resistance, high-temperature resistance was screened. To study the effect of E. faecium R1 on lipopolysaccharide (LPS)-induced intestinal and liver injury in piglets, twenty-four weaned female piglets were randomly assigned into one of three groups (8 piglets per group). Piglets in the control group and LPS group were fed a basal diet, piglets in the E. faecium group were fed the basal diet supplemented with E. faecium R1 (6.5 × 106 CFU/g). On day 21 of the trial, piglets in the LPS group and E. faecium group were intraperitoneally administered LPS (100 μg/kg), piglets in the control group were administered the same volume of saline. Subsequently, blood samples were collected at 3 h, and intestinal, liver, and pancreas samples were collected at 6 h. Results showed that E. faecium R1 supplementation significantly decreased the diarrhea rate and feed to gain ratio, and dramatically reduced LPS-induced intestinal and liver injury in piglets. Compared with the LPS group, E. faecium R1 supplementation significantly increased the content of glucagon in plasma and IL-1β in the liver, and the mRNA levels of villin in jejunum and ileum and Bcl-xL and pBD-L in the ileum, and significantly decreased the contents of prostaglandin 2 and malondialdehyde in the liver and the activities of myeloperoxidase and aspartate aminotransferase in plasma in piglets. Moreover, E. faecium R1 improved the pancreatic antioxidant capacity in piglets, which was indicated by a significant increase in catalase activity and a decrease in total nitric oxide synthase activity. In summary, dietary supplementation with E. faecium R1 alleviates intestinal and liver injury in LPS-challenged piglets.

L-arabinose Attenuates LPS-Induced Intestinal Inflammation and Injury through Reduced M1 Macrophage Polarization