桔梗皂苷-D对大鼠肝纤维化的干预作用及部分机制研究

Study on Effect and Mechanism of Platycodin D in Treating Experimental Liver Fibrosis in Rats

目的:研究桔梗皂苷-D(PD)对大鼠肝纤维化的干预作用及作用机制。方法:将大鼠随机分为5组,除对照组外,其余各组每周2次皮下注射四氯化碳(CCL4)溶液诱导肝纤维化模型,次日PD低剂量组、PD中剂量组、PD高剂量组分别给予PD 10、25、50 mg·kg-1·d-1灌胃持续给药治疗,对照组和模型组以等量0.9%氯化钠溶液代替。给药12周后,处死大鼠采集样本,检测各组大鼠血清ALT、AST、TNF-α、血清肝纤维指标(HA、LN、PIIIP、C-Ⅳ)水平;肝组织转化生长因子-β1(TGF-β1)、骨形成蛋白-7(BMP-7)、α-平滑肌肌动蛋白(α-SMA)mRNA的表达量;HE和天狼猩红染色观察肝组织病理学变化。结果:与模型组比较:PD各组能显著降低大鼠血清ALT、TNF-α、HA及肝组织TGF-β1mRNA水平,显著升高肝组织BMP-7mRNA水平(P<0.05);PD中剂量组和高剂量组能显著降低大鼠血清AST、LN及肝组织α-SMA mRNA水平(P<0.05);PD高剂量组能显著降低大鼠血清PIIIP、C-Ⅳ水平(P<0.05);肝组织纤维化程度明显改善。结论:PD具有抗肝纤维作用,并可能是通过降低TGF-β1和调高BMP-7的表达、抑制肝星状细胞的细胞增殖和活化,以达到抗纤维化的作用。

Objective：To investigate the effect and mechanism of Platycodin D （PD） in liver fibrosis. Methods：Fifty Wistar rats were divided into five groups. In addition to the control group,the rest groups were given subcutaneous injec- tion of the CC14 solution for 2 times per week to induce liver fibrosis model. PD - L, PD - M and PD - H groups were giv- en PD 10,25,50 mg kg-1 . d - 1 the next day, and the control and model groups were given 0.9% sodium chloride so- hltion to instead. The rats were killed after 12 weeks. ALT, AST,TNF -α,liver fiber marker （HA, LN, PIIIP, C - IV ） levels of rats serum and TGF- β1, BMP- 7, α-SMA mRNA expression quantity of liver tissue were tested. The patho- logical changes of liver tissue were observed by HE staining and Sirius red stain. Resttlts：Compared with model group, all PD groups can significantly reduce the levels of rats serum ALT,TNF - α,HA and liver tissue TGF - 131 mRNA and sig- nificantly increase tire level of liver tissue BMP -7 mRNA （P 〈 0.05 ）. PD -M and PD -H groups can significantly re- duce the levels of rats serum AST, LN and liver tissue of α - SMA mRNA （ P 〈 0.05 ）. PD - H group can significantly re- duce the level of rats serum PIIIP and C - IV （ P 〈 0.05 ）. The fibrosis states of rats liver tissue were significantly im- proved. Conclusion：PD can prevent liver fibrosis in rats by reducing the level of TGF - 131 and raising the level of BMP - 7 expression to inhibit HSCs profileration and activity.