【目的】观察益母草碱对乙型肝炎大鼠的治疗作用及机制。 【方法】将60只大鼠随机分为6组，即正常组，模型组，益母草碱低、中、高剂量组，益母草碱高剂量+溶血磷脂酸 （LPA） 组。除正常组外，其余各组大鼠构建乙型肝炎病毒 （HBV） 感染模型。造模成功后，各组对应干预。 干预结束后，采用酶联免疫吸附分析 （ELISA） 检测血清乙型肝炎e抗原 （HBeAg） 、乙型肝炎表面抗原 （HBsAg） 及炎症因子白细胞介素 （IL） -10、IL-6、肿瘤坏死因子α （TNF-α） 水平，自动分析仪测定血清丙氨酸氨基转移酶 （ALT） 、天门冬氨酸氨基转移酶 （AST） 水平，实时定量聚合酶链反应 （RT-qPCR） 法检测肝组织HBV DNA水平，苏木素-伊红 （HE） 染色法观察肝组织病理变化，免疫组织化学法检测肝组织乙型肝炎核心抗原 （HBcAg） 表达水平，Western Blot法检测肝组织Ras同源基因家族成员A （RhoA） 、 Rho相关卷曲螺旋蛋白激酶 （ROCK） 1、ROCK2表达水平。 【结果】与正常组比较，模型组大鼠肝小叶中心坏死，肝细胞水肿、变性，HBsAg、HBeAg、HBV DNA水平，HBcAg阳性细胞数，ALT、AST水平，IL-6、TNF-α、IL-10含量，RhoA、ROCK1、ROCK2表达水平均显著升高 （均P＜0.05） ；与模型组比较，益母草碱低、中、高剂量组大鼠肝损伤程度降低，肝细胞变性减轻，HBsAg、HBeAg、HBV DNA水平，HBcAg阳性细胞数，ALT、AST水平，IL-6、TNF-α含量，RhoA、ROCK1、ROCK2表达水平均显著降低，IL-10含量升高，差异均有统计学意义 （P＜0.05） ；与益母草碱高剂量组比较，益母草碱高剂量+LPA组肝损伤程度加重，HBsAg、HBeAg、HBV DNA水平，HBcAg阳性细胞数，ALT、AST水平，IL-6、TNF-α含量，RhoA、ROCK1、ROCK2表达水平升高，IL-10含量降低，差异均有统计学意义 （P＜0.05） 。 【结论】益母草碱能减轻乙型肝炎大鼠肝组织损伤，改善肝功能，减少炎症反应，其机制与抑制RhoA/ROCK通路有关。

Objective To observe the therapeutic effect and mechanism of Leonurine on hepatitis B rats. Methods Sixty rats were randomly divided into six groups，i.e.，the normal group，the model group，the Leonurine low-，medium- and high- dose groups，and the Leonurine high-dose + lysophosphatidic acid （LPA） group. Hepatitis B model was constructed for rats in all groups except for the normal group. After successful modeling，each group was given corresponding invention. At the end of administration，the levels of serum hepatitis B e antigen （HBeAg） ，hepatitis B surface antigen （HBsAg），and inflammatory factors such as interleukin （IL）-10，IL-6 and tumor necrosis factor α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA） ，and levels of serum alanine aminotransferase （ALT） and aspartate transaminase （AST） were detected by automatic analyzer. Real-time fluorescence quantitative PCR （qRT-PCR） was used to detect HBV DNA level in liver tissues，hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissues，immunohistochemistry was used to detect the expression of hepatitis B core antigen （HBcAg） in liver tissues，and Western Blot was used to detect the expression of Ras homolog gene family member A （RhoA）， Rho-associated coiled-coil containing kinases （ROCK） 1 and ROCK2. Results Compared with the normal group，necrosis in the center of hepatic lobules ，edema and degeneration of hepatocytes in rats was showed in the model group，and the levels of HBsAg，HBeAg and HBV DNA，HBcAg-positive cell counts，the levels of ALT and AST，the contents of IL-6，TNF-α and IL-10，and the expression levels of RhoA，ROCK1，ROCK2 were significantly increased （all P＜0.05） . Compared with the model group，liver damage degree was decreased and cellular degeneration was reduced in rats in the Leonurine low-，medium- and high- dose groups，the levels of HBsAg，HBeAg and HBV DNA，HBcAg-positive cell counts，the levels of ALT and AST，the contents of IL-6 and TNF-α，and the expression levels of RhoA，ROCK1 and ROCK2 were significantly decreased，and the IL-10 level were significantly increased，the differences being statistically significant （P＜0.05） . Compared with the Leonurine high-dose group，the degree of liver damage was increased in the Leonurine high-dose +LPA group，the levels of HBsAg，HBeAg and HBV DNA，HBcAg-positive cell counts，the levels ALT and AST，contents of IL-6 and TNF-α，and the expression levels of RhoA，ROCK1 and ROCK2 were significantly increased，and IL-10 level was significantly decreased，the differences being statistically significant（P＜0.05） . Conclusion Leonurine can relieve liver injury，improve liver function and reduce inflammatory reaction in hepatitis B rats，and its mechanism is related to the inhibition of RhoA/ROCK pathway.

R285.5

河北省医学科学研究课题计划项目 （编号：20241127）