归芍颗粒对四氯化碳诱导的大鼠肝纤维化的保护作用

Protective Efficacy of Guishao Granules on Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats

目的:观察归芍颗粒(Guishao granules,GG)对四氯化碳(carbon tetrachloride,CCl4)诱导的SD大鼠肝纤维化的作用。方法:90只雄性SD大鼠,除正常组15只不造模外,其余大鼠背部ih CCl4(1 m L·kg-1),每周2次,共13周制备肝纤维化模型,随机分为5组,分别为模型组,GG低、中、高剂量组(3.5,7.0,14 g·kg-1)和秋水仙碱组(0.1 mg·kg-1),每组15只。13周后,测定大鼠肝脏指数;取部分肝组织做苏木素-伊红(HE)和马松三色(Masson)染色;取血测血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的活性;放射免疫法检测血清中透明质酸(HA)和层粘连蛋白(LN)的水平;分光光度法检测大鼠肝脏中羟脯氨酸(Hyp)含量;免疫组化法检测肝脏中α-平滑肌肌动蛋白(α-SMA)的表达水平。结果:与正常组比较,模型组大鼠肝损伤,肝纤维化程度明显,肝纤维化大鼠血清中ALT,AST和HA,LN水平明显升高,肝组织中Hyp的含量明显升高,肝组织中α-SMA蛋白的表达明显升高(P<0.05,P<0.01);GG能明显改善大鼠肝损伤,减轻肝纤维化程度,同时显著降低肝纤维化大鼠血清中ALT,AST和HA,LN水平,GG能降低肝组织中Hyp的含量,抑制肝组织中α-SMA蛋白的表达(P<0.05,P<0.01)。结论:GG可以明显改善CCl4诱导的大鼠肝纤维化,其作用机制可能与GG抑制肝星状细胞活化有关。

Objective： To investigate the efficacy of Guishao granules（ GG） on hepatic fibrosis induced by carbon tetrachloride（ CCl4） in SD rats. Method： In 90 male SD rats,15 of them were used as the normal group,and other rats were used to induce hepatic fibrosis models by subcutaneously injecting with CCl4（ 1 m L·kg- 1）,two times / week for a total of 13 weeks. The rats were randomly divided into model group,GG low dose group,middle dose group,high dose group（ 3. 5,7. 0,14 g·kg- 1） and colchicine group（ 0. 1 mg·kg- 1）,n = 15 in each group. After 13 weeks,liver indexes of the rats were detected; partial liver tissues were taken for hematoxylineosin（ HE） staining and Masson staining. Blood was taken to measure the activities of serum alanine aminotransferase（ ALT） and aspartate aminotransferase（ AST）. Levels of hyaluronic acid（ HA） and laminin（ LN） in serum were detected by radioimmunoassay. The levels of hydroxyproline（ Hyp） in liver of rats were measured by spectrophotometric method and the expression of α-smooth muscle actin（ α-SMA） in liver was detected by immunohistochemistry method. Result： Compared with the normal group, liver injury and hepatic fibrosis were obvious in the rats of model group; the levels of ALT, AST, HA and LN in the serum were significantly increased in the rats with liver fibrosis; the level of Hyp in liver tissues were significantly increased;and the expression of α-SMA protein in liver tissues was significantly increased（ P〈 0. 05,P〈 0. 01）. GG could significantly improve liver injury of rats,reduce hepatic fibrosis,significantly reduce the levels of ALT,AST,HA,and LN in the serum of model rats,decrease the level of Hyp in liver tissues,and inhibit the expression ofα-SMA protein in liver tissues of the model rats（ P〈 0. 05, P〈 0. 01）. Conclusion： GG could significantly attenuate hepatic fibrosis induced by CCl4 in rats, and its mechanism may be associated with inhibiting the activation of hepatic stellate cells.