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抗纤维化草药与硒对肝纤维化大鼠的治疗作用及分子机制

Therapeutic effects and molecular mechanisms of anti-fibrosis herbs and selenium on rats with hepatic fibrosis.

作者信息

He Yu-Tong, Liu Dian-Wu, Ding Li-Yu, Li Qing, Xiao Yong-Hong

机构信息

Department of Epidemiology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.

出版信息

World J Gastroenterol. 2004 Mar 1;10(5):703-6. doi: 10.3748/wjg.v10.i5.703.

Abstract

AIM

To study the therapeutic effects of anti-fibrosis herbs and selenium on hepatic fibrosis induced by carbon tetrachloride (CCl(4)) in rats and the underlining molecular mechanisms.

METHODS

Fifty-three Wistar rats were randomly divided into: normal control group, model control group, colchicine group, anti-fibrosis herbs group (AF group) and anti-fibrosis herbs plus selenium group (AS group). The last four groups were administered with CCl(4) at the beginning of experiment to induce hepatic fibrosis. Then colchicine, anti-fibrosis herbs and selenium were used to treat them. The normal control group and the model control group were given normal saline at the same time. At the end of the 6(th) week, rats in each group were sacrificed. Blood and tissue specimens were taken. Serum indicators (ALT, AST, HA, LN) were determined and histopathological changes were graded. Lymphocyte CD(4) and CD(8) were examined by flow cytometry. Expression of TGF-beta(1) and NF-kappaB was detected by immunohistochemistry and expression of TGF-beta(1) mRNA was detected by semi-quantified RT-PCR.

RESULTS

Histological grading showed much a smaller degree of hepatic fibrogenesis in AS group and AF group than that in colchicine group and model control group. The serum content of ALT, AST, HA and LN in AF group and AS group were significantly lower than that in colchicine group (ALT: 65.8+/-26.5, 67.3+/-18.4 and 96.2+/-20.9 in AF, AS and colchicine groups respectively; AST: 150.8+/-34.0, 154.6+/-27.3 and 215.8+/-24.6 respectively; HA: 228+/-83, 216+/-58 and 416+/-135 respectively; LN: 85.9+/-15.0, 80.6+/-18.6 and 106.3+/-14.2 respectively) (P<0.05). The level of CD(4) and CD(4)/CD(8) ratio in AF group and AS group was significantly higher that those in cochicine group (CD(4): 50.8+/-3.8, 52.6+/-3.4 and 40.2+/-2.1 in AF, AS and colchicine groups respectively; CD(4)/CD(8) ratio: 1.45, 1.46 and 1.26, respectively (P<0.05). The expression level of NF-kappaB and TGF-beta(1) in the liver tissues of AF and AS treatment groups was markedly decreased compared with that in cochicine group, and TGF-beta(1) mRNA was also markedly decreased (1.07+/-0.31 and 0.98+/-0.14 vs 2.34+/-0.43, P<0.05).

CONCLUSION

Anti-fibrosis herbs and selenium have beneficial effects on hepatic fibrosis in rats by enhancing immunity and inhibiting NF-kappaB and TGF-beta(1) expressions.

摘要

目的

研究抗纤维化中药及硒对四氯化碳(CCl₄)诱导的大鼠肝纤维化的治疗作用及其潜在分子机制。

方法

53只Wistar大鼠随机分为:正常对照组、模型对照组、秋水仙碱组、抗纤维化中药组(AF组)和抗纤维化中药加硒组(AS组)。后四组在实验开始时给予CCl₄诱导肝纤维化。然后分别用秋水仙碱、抗纤维化中药和硒进行治疗。正常对照组和模型对照组同时给予生理盐水。在第6周结束时,处死每组大鼠,采集血液和组织标本。测定血清指标(谷丙转氨酶、谷草转氨酶、透明质酸、层粘连蛋白)并对组织病理学变化进行分级。采用流式细胞术检测淋巴细胞CD4和CD8。通过免疫组织化学检测转化生长因子β1(TGF-β1)和核因子κB(NF-κB)的表达,通过半定量逆转录聚合酶链反应检测TGF-β1 mRNA的表达。

结果

组织学分级显示,AS组和AF组肝纤维化程度明显低于秋水仙碱组和模型对照组。AF组和AS组血清谷丙转氨酶、谷草转氨酶、透明质酸和层粘连蛋白含量明显低于秋水仙碱组(AF组、AS组和秋水仙碱组谷丙转氨酶分别为65.8±26.5、67.3±18.4和96.2±20.9;谷草转氨酶分别为150.8±34.0、154.6±27.3和215.8±24.6;透明质酸分别为228±83、216±58和416±135;层粘连蛋白分别为85.9±15.0、80.6±18.6和106.3±14.2)(P<0.05)。AF组和AS组CD4水平及CD4/CD8比值明显高于秋水仙碱组(AF组、AS组和秋水仙碱组CD4分别为50.8±3.8、52.6±3.4和40.2±2.1;CD4/CD8比值分别为1.45、1.46和1.26,P<0.05)。与秋水仙碱组相比,AF组和AS组肝组织中NF-κB和TGF-β1的表达水平明显降低,TGF-β1 mRNA也明显降低(分别为1.07±0.31和0.98±0.14,对比2.34±0.43,P<0.05)。

结论

抗纤维化中药及硒通过增强免疫力、抑制NF-κB和TGF-β1表达对大鼠肝纤维化具有有益作用。

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