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OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.
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Fibrosis is an important pathoIogicaI change in a variety of diseases and with compIicated causes. Fibrosis diseases in different organs have different causes,but the common manifestations of fibrobIast are proIiferation and coIIagen deposition that couId eventuaIIy Iead to normaI tissue damage and Ioss of function. Fibrosis in such important organs as the heart or Iung couId be Iife-threatening. There are different reguIating factors and drugs to fibrosis. Chinese medicine treatment is stiII the main method cIinicaIIy for Iiver fibrosis. Because there is no effective cure for puImonary fibrosis,treatment focuses on anti-infIammation by aIIeviating Iesion and improving kidney function. Despite the tremendous progress in fibrosis treatment,there is stiII a Iack of targeted drugs that couId cure a specific disease in a specific area. With the deveIopment of gene technoIogy,gene therapy wiII become an important treatment for this disease. This paper introduces anti-myocardiaI fibrosis drugs according to the mechanism.
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Acetaminophen(APAP)is the most wideIy-used anaIgesic drug cIinicaIIy. It is aIso the most risky agent for hepatotoxicity. It has been wideIy used as a modeI drug to study mechanisms of chemicaI-induced Iiver injury and to test the hepatoprotective potentiaI of chemicaIs. This review summa-rized the intraceIIuIar events of acetaminophen-induced hepatotoxicity,incIuding metaboIic activation, ceIIuIar damage,c-Hun N-terminaI kinase pathway,and modified metaboIism function,and additionaIIy focused on the roIe of infIammatory factors and ceIIs in APAP hepatotoxicity,as weII as protection strate-gies of chemicaIs and naturaI products.
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OBJECTlVE To study the preventive effect of vitamin E(Vit E)on chronic Iiver injury in-duced by N,N-dimethyIformamide( DmF). METHODS HeaIthy maIe Kunming mice were randomIy divided into 4 groups,10 mice in each group. The mice in DmF modeI group and DmF+Vit E group were ig given DmF 0.5 g·kg-1 ,whiIe Vit E controI group and DmF+Vit E group were ig given Vit E 5 mg·kg-1 after 2 h once a day for 30 d. The activity of serum gIutamic-oxaIoacetic transaminase(GOT),gIutamic-pyruvic transaminase(GPT)and xanthine oxidase(XOD)and the content of maIondiaIdehyde(mDA) in Iiver tissue were measured with corresponding kits. The pathoIogicaI changes of Iiver tissue were ob-served with HE staining. RESULTS Compared with the normaI controI group,the activity of serum GOT,GPT and XOD of the DmF modeI group was significantIy eIevated(P﹤0.05,P﹤0.01),and the Iiver ceII nucIeus pycnosis,ceIIuIar edema,degeneration,necrosis occurred. Compared with DmF modeI group,the activity of serum GOT,GPT and XOD of DmF+Vit E group were aII significantIy reduced(P﹤0.05,P﹤0.01),the content of mDA in Iiver tissue was significantIy diminished(P﹤0.01),but histopatho-IogicaI changes of Iiver tissue were significantIy improved. CONCLUSlON Vit E has preventive effect on chronic Iiver damage induced by DmF through antioxidation.
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ObjectiveTo investigate the therapeutic effect of mefformin on type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD).MethodsThe model rats of T2DM complicated with NAFLD were established by feeding high-glucose and high-fat diet, and injection of low dose streptozotocin.The model rats were randomly divided into 2 groups, model group (n = 16) and metformin group (n = 16).Twenty normal rats were set for normal control group.Intragastric administration lasted for 12 weeks.At the end of 16th week (after treated 8 weeks) and 20th week (after treated 12weeks), the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), fasting blood glucose (FBG),fasting insulin (FINs), triglyceride (TG), total cholesterol (TC) and free fatty acid (FFA) in each group were determined and the level of insulin sensitivity index (ISI) was determined.Meanwhile, pathological changes of liver, the expression of uncoupling protein-2 (UCP-2) mRNA and UCP-2 protein of liver tissues in each group were detected.ResultsThe levels of serum ALT, AST, FBG,FINs, serum TG , TC and FFA were significantly higher and ISI was significantly lower and the expression of UCP-2 protein significantly increased in model group, compared with control group (all P ＜ 0.01).The expression of UCP-2 mRNA at 16th and 20th week in model group were significantly higher than that in control group [(1.789 +0.301) vs (0.245 ±0.087), t =11.02, P ＜0.01 and (1.989 +0.207) vs (0.262+ 0.058), t = 17.93, P ＜ 0.01, respectively].Fatty degeneration of liver tissues was significantly exacerbated in model group.After treatment for 8 weeks and 12 weeks with mefformin, the levels of serum ALT,AST, FBG, serum TG, TC and FFA significantly decreased, ISI significantly increased, fatty degeneration of liver tissues was significantly improved, and the expression of UCP-2 protein significantly decreased,compared with model rats (P ＜ 0.01 or P ＜ 0.05).The expression of UCP-2 mRNA at 16th and 20th week in metformin group were significantly lower than that in model group [(0.665 + 0.088) vs (1.789 ±0.301), t = 7.81, P ＜ 0.01 and (0.610 ± 0.1 02) vs (1.989 ± 0.207), t = 9.98, P ＜ 0.01, respectivelv].ConclusionsMetformin has therapeutic effect on T2DM complicated with NAFLD.
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Objective To provide a technique of preparation recombinant hALR by gene engineering in larger scale.Methods Construct hALR(human augmenter of liver regeneration) protein expression vector pGEX-3X-hALR,induce the expreesion of hALR,and pruified the protein by affinity chromatography.Results Succeed in constructing the vector pGEX-3X-hALR and obtained the recombinant hALR protein.Conclusion The mothed could be used for preparation recombinant hALR by gene engineering in larger scale.
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Objective To investigate dynamic changes of heme oxygenase-1 and carbon monoxide in acute liver injury induced by carbon tetrach loride(CCl_4)in rats.Method Male SD rats were randomly allocated to induce acute liver injury by CCl_4 injection.Hepatic HO activity was examined at different time point following CCl_4 treatment.Expression and location of HO-1 protein was determined by western blot and immunohistochemical methods.Serum ALT,AST levels and hepatic SOD,MDA concentrations were also analyzed.Results Administration of CCl_4 to rats caused a marked hepatic damage,characterized by significant elevation of serum ALT,AST levels and liver MDA content combined with a remarkable reduction in liver SOD activity.HO activity was elevated significanfly in a time-dependant manner after CCl_4 injection,while the expression of HO-1 protein increased remarkably from 6 to 36 hours.CO concentration in the liver homogenate of control rats remained very low but was elevated significantly after CCl_4 treatment,which was in accordance with changes of HO-1. Conclusions HO-1 activity and protein expression as well as CO production are higher in rats with acute liver injury induced by CCl_4 than in control group.HO-1/CO system plays an important role in the pathogenesis of acute hepatic damage and may have potent protective effect against liver injury.
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During the past five years, 141 cases of liver cirrohosis were hospitalized intoour clinic. The mean age of these patients was 57.8 years old, and the ratio of male to female was 2.8 to 1. HBs antigen was positive in 16 cases, and among the patients without HBs antigen 49 cases of heavy alcoholic drinker were found. Seventy patients with liver cirrhosis were dividedinto a compensatory group and a decompensatory group according to three clinical findings, ascites, hepatic encephalopathy and bleeding from gastrointestinal tract. It was suggested that five items of biochemical data for liver function were very important on discriminating these two groups. The five items were cholinesterase, indocyanine green test, albumin, prothrombin time and erythrocyte count.<BR>Next, we studied clinical findings of eight patients with minute hepatocellular carcinoma hospitalized into our clinic during the past five years. About a definition of minute hepatocellular carcinoma, we have defined that the tumor size should be less than 3 cm in diameter. Six of these patients were male, and average age was 56.7 years old. Of these patients, five were complicated by liver cirrhosis, and only one revealed positive HBs antigen in serum. The serum alpha-fetoprotein level showed more than 400 ng/ml in three patients. And we have thought that ultrasonographic examination is most effective to diagnose minute hepatocellular carcinoma in various diagnostic imaging methods. Most of patients exhibited a decreased functional reserve in the liver, but six patients underwent hepatic resection. After operation, one patient died of acutehepatic insufficiency on the 8th day, and one died of the recurrence of tumor on the 11th month. Otherfour patients have been alive now.