AIM: To investigate the protective effects of berberine against liver injury induced by lipopolysaccharide in mice and the mechanisms underlying its protective effect.METHODS: The male mice were divided randomly into control,berberine group,LPS group and berberine treatment group.Mice were administered intragastrically with distilled water(0.01 mL/g) or(5 g/L) neutral sulfate berberine(0.01 mL/g) once a day for 5 days and injected intraperitoneally with normal saline or LPS(0.02(mL/g),28 mg/kg)at 1 h after gavage on day 5.Blood was collected for determining alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activities,the content of tumor necrosis factors-?(TNF-?) at 10 h and 2 h after LPS or normal saline injection,respectively.Furthermore,the liver tissue was processed,and histological changes and ultrastructure in liver were observed with light and electron microscopy,malondialdehyde(MDA) content and superoxide dismutase(SOD) activity in liver were also detected.RESULTS: Both ALT and AST activities in serum in LPS group were higher than those in control and berberine treatment group.LPS increased the serum TNF-? content at 2 h after injection,which was reversed by berberine pretreatment.The histological examination showed that LPS caused severe hepatic cell edema,degeneration,apoptosis and even necrosis,and ultrastructure observation demonstrated that LPS induced mitochondrial swelling,condensation and margination of chromatin,irregular nuclear envelope in hepatocytes.The above pathological changes produced by LPS were attenuated by berberine pretreatment.Moreover,MDA contents in liver tissue were higher in LPS group than control and berberine treatment group,but there were no significant difference in SOD activity between berberine treatment and LPS group.CONCLUSION: Berberine has a protective effect on LPS-induced liver injury in mice,the mechanisms may be related to its decreasing the production of TNF-?,inhibiting lipid peroxidation and protecting mitochondria.

AIM: To investigate the mechanisms by which berberine attenuates LPS-induced acute lung injury, and provide a new strategy for the treatment of the lung injury due to LPS. METHODS: BALB/c mice were randomly assigned into three groups (control, LPS group, and berberine treatment group). Mice were administered intragastrically with distilled water (0.1 mL/10 g) or neutral sulfate berberine (50 mg/kg) once a day for 3 days, 1 h after intragastrical treatment on day 3, LPS (20 mg/kg) or normal saline was injected intraperitoneally (ip). All animals were sacrificed 12 h after LPS injection, the left lung tissue sections were prepared for histology analysis and the right lung were used to determine the ratio of wet to dry lung tissue weight (W/D). In another experiment, bronchoalveolar lavage fluid (BALF) was collected, and then the total protein content, and the amounts of white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in BALF were determined. Furthermore, the phosphorylation of cytosolic phospholipase A2 (cPLA2) was detected with immunohistochemical analysis by using phospho-cPLA2(Ser505) antibody, and the contents of thromboxane B2 (TXB2) in BALF, malondialdehyde (MDA) in the lungs, and activity of superoxide dismutase (SOD) in lung tissues were also determined.RESULTS: LPS induced acute lung injury, activated cPLA2, and increased TXB2 content in the BALF and MDA level in the lung tissue. The pretreatment with berberine significantly attenuated lung injury, lung edema and protein leakage induced by intraperitoneal injection of LPS. The expression of phospho-cPLA2 in the lung tissues and TXB2 content in the BALF in the berberine treatment group were lower than those in LPS group (P0.05). CONCLUSION: Pretreatment with berberine remarkably reduces the LPS-induced lung injury, which is, at least in part, through inhibiting phosphorylation of cPLA2 and decreasing lipid peroxidation. These findings provide a new strategy for the prevention and treatment of LPS-induced acute lung injury.

OBJECTIVE:To study the protective effect of fingolimod on renal ischemia reperfusion injury (RIRI) model mice and its mechanism.METHODS:A total of 60 mice were randomly divided into sham operation group,model group,fingolimod group (1 mg/kg) and fingolimod+wortmannin group [fingolimod 1 mg/kg+phosphatidylinositol 3-kinase (PI3K) specific blocker wortmarmin 1.4 mg/kg],with 15 mice in each group.Except for sham operation group,RIRI model was induced in other 3 groups,and those model mice were given relevant medicine via caudal vein at once 24 h before surgery.Serum of mice were collected in each group after 24 h perfusion.Serum levels of Scr and BUN were measured by automatic biochemical analyzer.The pathological changes of renal tissue were observed under light microscope.The protein expression of intercellular cell adhesion molecule-1 (ICAM-1),monocyte chemoattractant protein-1 (MCP-1) and phosphorylated protein kinase B (p-Akt) in renal tissue were measured by Western blot assay.RESULTS:Compared with sham operation group,the serum levels of Scr and BUN in model group were increased significantly (P＜0.01).Pathological changes were found in the kidney,and RIRI led to widespread renal tubular epithelial cell injury,apoptosis and inflammatory cells infiltration.The protein expression of ICAM-1 and MCP-1 in renal tissue were increased significantly (P＜0.01),the protein expression of p-Akt was increased slightly (P＞0.05).Compared with model group,other indexes of fingolimod group were improved significantly (P＜0.01) except that the protein expression of p-Akt in renal tissue was increased significantly (P＜0.01).Compared with fingolimod group,above indexes of fingolimod+wortmannin group were reversed (P＜0.05 or P＜0.01).CONCLUSIONS:Fingolimod can obviously ameliorate renal injury induced by RIRI in mice,the mechanism of which may be associated with the activation of PI3K/Akt signaling pathway.

OBJECTIVE： To study on the effects of prophylactic administration of Ramulus mori polysaccharides （RMP） on inflammatory response of renal ischemia reperfusion injury （RIRI） model mice and to explore its possible mechanism. METHODS： Totally 60 C57BL/6 mice were randomly divided to sham operation group， model group， atorvastatin group （positive control， 15 mg/kg）， RMP low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg）. Except for sham operation group， RIRI model was induced in other 5 groups. 24 h before surgery， they were given relevant medicine intragastrically， once a day， for consecutive one week. 24 h after reperfusion， the mice were sacrificed. The serum levels of Scr and BUN were detected. The morphological changes of renal tissue were observed under optical microscope. The serum levels of IL-1β， IL-6， IL-10 and TNF-α were determined by ELISA. Western blot assay was used to determine the protein expressions of Toll-like receptor 4 （TLR4）， p38 mitogen-activation protein kinase （p38MAPK） and p-p38MAPK. RESULTS： Compared with sham operation group， the serum levels of Scr and BUN were significantly elevated in model group  （P＜0.01）. RIRI led to typical inflammatory response of renal tissue， widespread renal tubular epithelial cell degeneration and necrosis， and inflammatory cells infiltration. Serum levels of IL-1β， IL-6， IL-10 and TNF-α were increased significantly （P＜0.01）. The protein expressions of TLR4， p38MAPK and p-p38MAPK were increased significantly in renal cortex （P＜0.01）. Compared with model group， serum levels of Scr and BUN were decreased significantly in administration groups （P＜0.05 or P＜0.01）. The pathological damage of renal tissue was improved in varying degrees， especially in the RMP medium-dose and high-dose groups. Serum levels of IL-1β and IL-6 were decreased significantly in administration groups （P＜0.05 or P＜0.01）. Serum levels of IL-10 were further increased in atorvastatin group and RMP high-dose group （P＜0.01）， and serum level of TNF-α was decreased significantly in atorvastatin group and RMP medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The protein expressions of TLR4 and p-p38MAPK in renal cortex were decreased significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS： RMP prophylactic administration can improve RIRI of mice， the mechanism of which may be associated with relieving the inflammatory response through inhibition of TLR4/p38MAPK signaling pathway.