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Jade Lang Umbrella Flavonoids On The Protective Effect And Mechanism Of Liver Injury

Posted on:2013-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y J GuoFull Text:PDF
GTID:2244330371474659Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective:To observe the protective effects of Yulangsan flavonoids (YLSF) on acute chemical liver injurise by CC14, AP and D-Gal N in mice.Methods:The models of CC14, AP and D-GalN induced acute liver injury in mice with the method of intraperitoneal injection were used to study the liver protective effects of YLSF.The Kunming mice were divided into normal control group (NC), model group (MC), high-, medium-and low-doses of YLSF groups, and positive control group (Biphenyldicarboxylate group, DDB). The mice of NC and MC groups were treated with NS, and all doses of YLSF groups and the positive control group were treated with YLSF (112,56,28mg/kg) and DDB (150mg/kg) respectively. All mice were treated with drugs or NS for7conse-cutive days ig, qd.1hour after the last administration of drugs, each group of mice was induced by CC14(0.1%), AP(300mg/kg) or D-GalN(800mg/kg), ip, respectively, except the NC group. The activities of AST, ALT and ALP, the content of Alb, the ability of T-AOC in serum, the content of MDA, and the activity of SOD in liver tissue were investigated by spectrophotometry, and the degree of hepatic injury was examined.Results:(1) In CCl4induced mice acute chemical liver injur, each dose of YLSF could extenuate the degree of hepatic injury (P<0.05or P<0.01). The indexes of thymus, spleen and liver were reduced (P<0.05or P<0.01), the activities of AST, ALT and ALP in serum and the content of MDA in liver were de-creased (P<0.01), meanwhile the content of Alb and the activity of T-AOC in serum and the ability of SOD in liver were enhanced (P<0.01) obviously by treatment with medium-and high-doses of YLSF. Then the indexes of thymus, spleen were reduced, the activities of AST, ALP in serum and the content of MDA in liver were decreased (P<0.05or P<0.01), at the same time,the content of Alb in serum was increased (P<0.01) by treated with low dose of YLSF.(2) In AP induced mice acute chemical liver injury, each dose of YLSF could reduce the index of liver and the activities of AST, ALT, ALP in serum, could increase the content of Alb in serum (P<0.05or P<0.01). The index of spleen, activity of ALT in serum, content of MDA in liver were decreased (P<0.05or P<0.01), and the degree of hepatic injury were lessened obviously by treated with medium-and high-doses of YLSF. And then the ability of T-AOC in serum and the activity of SOD in liver were enhanced (P<0.01) obviously by treated with low dose of YLSF. (3) Then in D-GalN induced mice acute chemical liver injury, each dose of YLSF could decrease the activities of ALT, AST, ALP in serum (P<0.01) and the content of MDA in liver, meanwhile increase (P<0.01) the content of Alb in serum. The level of T-AOC in serum and the activity of SOD in liver were increased (P<0.01), and the degree of hepatic injury were lessened (P<0.01) obviously by treated with medium-and high-doses of YLSF. At the same time, the index of thymus was lessened significantly by treated with high-dose of YLSF.Conclusions:YLSF has protective effects on acute chemical liver injury. The mechanism may be related to attenuating free radical and inhibiting the effect on lipid peroxidation. Objective:The aim of our study is to investigate the effects of Yulangsan flavonoids (YLSF) against CCl4-induced liver fibrosis in rats and study its mechanism.Methods:The SD rats were divided into two groups randomly:hepatic fibrosis group and normal control group(NC). The rats of hepatic fibrosis group were induced by intragastric administration (i.g.) of50%CCl4, and the those of NC group were given normal saline (NS). The rats of hepatic fibrosis group confirmed by the pathological inspection were divided into2groups randomly: Drug intervention group and the model group which were treated with NS. The drug intervention group was divided randomly into3different does YLSF groups (20mg/kg,40mg/kg and80mg/kg) and a positive control group (colchicine tablets0.20mg/kg). All rats were treated with drugs or NS for four consecutive weeks ig, one time a day.(1) The behavior, diet, mental state and survival quantity of rats were observed and recorded.24hours after the last administration of drugs, all rats were sacrificed, and the blood serum and hepatic tissue were taken quickly. The activities of ALT and AST in the serum and the levels of SOD, MDA, GSH, and GSH-Px in hepatic tissue were analyzed, the indexes of liver, spleenand thymus were counted.pieces Of hepatic tissues in the identical spot of liver,size (1×1×1) cm3were taken and soaked in10%Formaldehyde solution. Then the degree of hepatic injury was examined with HE staining.(2) The relative quantification of Col-Ⅰ, TIMP-1and TGF-β1mRNA ex-pression in hepatic tissues were detected by RT-PCR.Results(1) After the treatment in a month, the survival probability of rats in each dose YLSF group and positive medicine group were Higher than the model group. And compared with the model control group, the increased activity of AST in serum and the increased content of MDA in liver induced by CCl4were decreased significantly, and the decreased levels of SOD in liver was increased significantly in all dose of YLSF groups and positive control group. The activity of ALT in serum was decreased significantly (P<0.01) and the content of GSH (P<0.01) in liver was increased in the high dose and the middle dose of YLSF groups and positive control group. Meanwhile the activity of GSH-Px in the liver was increased significantly in the high dose and the middle dose of YLSF groups (P<0.01).(2) In all dose of YLSF groups and positive control group, the relative quantification of Col-Ⅰ, TIMP-1and TGF-β1mRNA expression could be decreased (P<0.01),and the degree of hepatic injury could be lessened (P<0.05or P<0.01). Conclusion:Our findings demonstrate that YLSF has a certain curative effect on CCl4-induced liver fibrosis in rats, and its mechanisms maybe involve in attenuating free radical, inhibiting the lipid peroxidation and the incentive of Extracellular matrix(ECM),and producing the degradation of ECM. Objective:To observe the effects of Yulangsan flavonoids (YLSF) and the rats serum containing Yulangsan flavonoids (medicated serum) on the proliferation of HSC-T6Method:HSC-T6were cultured in vitro, and MTT assay was used to evaluate the inhibitive effect of YLSF.Result:YLSF could obviously inhibit the proliferation of HSC-T6(P<0.05).Conclusion:The mechanism of liver fibrosis inhibited by YLSF may attribute to that YLSF suppressed the proliferation of HSC-T6.
Keywords/Search Tags:yulangsan, flavonoids, acute chemical liver injury, antioxidation, miceyulangsan flavonoids, liver fibrosis, Col-Ⅰ, TIMP-1, TGF-β1yulangsan, HSC-T6, cell proliferation
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