College of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China.
College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China.
J Tradit Chin Med. 2021 Feb;41(1):79-88. doi: 10.19852/j.cnki.jtcm.2021.01.010.
To investigate the efficacy of Cigu Xiaozhi pill (, CGXZ) on non-alcoholic steatohepatitis (NASH)-associated lipoapoptosis through the stress-activated c-Jun N-terminal kinase (JNK)/ stress-activated protein kinase signalling pathway.
Sixty male Sprague-Dawley rats were randomly divided into the following groups (10rats each): blank control, model, low-dose CGXZ, medium-dose CGXZ, high-dose CGXZ, and positive control (treated with SP600125, a JNK inhibitor). The NASH model was established and the histomorphological characteristics of haematoxylin and eosin-stained liver tissues were examined under a light microscope. Cell apoptosis in liver tissues was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labelling assay. In addition, the mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L were determined via fluorescence-based quantitative real-time PCR, immunohistochemical and Western blot assays.
Histopathological examination of the liver showed that the model rats had moderate-to-severe steatosis with infiltration of inflammatory cells as well as significantly higher expression levels of the p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L proteins, compared with those in the blank control group (P < 0.01). Hepatic lobules of the rats in the treatment groups showed significantly reduced vacuolar degeneration and steatosis as well as alleviated inflammatory cell infiltration. The high and medium-dose CGXZ groups exhibited significantly lower mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, compared with those in the model group (P < 0.05 or P < 0.01).
CGXZ pill inhibited the onset of hepatocyte apoptosis by regulating the expression of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, thereby exerting therapeutic effects against NASH.
通过应激激活的 c-Jun N 末端激酶（JNK）/应激激活蛋白激酶信号通路，研究刺蒺藜消痔丸（CGXZ）对非酒精性脂肪性肝炎（NASH）相关脂肪凋亡的疗效。
将 60 只雄性 Sprague-Dawley 大鼠随机分为以下几组（每组 10 只）：空白对照组、模型组、CGXZ 低剂量组、CGXZ 中剂量组、CGXZ 高剂量组和阳性对照组（用 JNK 抑制剂 SP600125 治疗）。建立 NASH 模型，用苏木精-伊红染色法在光镜下观察肝组织的组织形态学特征。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记法评估肝组织细胞凋亡。此外，通过荧光定量实时 PCR、免疫组织化学和 Western blot 检测法，测定 p-JNK、p-c-Jun、caspase-8、Fas 和 Fas-L 的 mRNA 和蛋白表达水平。
肝组织病理学检查显示，模型组大鼠出现中重度脂肪变性，伴有炎症细胞浸润，p-JNK、p-c-Jun、caspase-8、Fas 和 Fas-L 蛋白表达水平明显高于空白对照组（P < 0.01）。治疗组大鼠肝小叶空泡变性和脂肪变性明显减轻，炎症细胞浸润减轻。CGXZ 高、中剂量组 p-JNK、p-c-Jun、caspase-8、Fas 和 Fas-L 的 mRNA 和蛋白表达水平明显低于模型组（P < 0.05 或 P < 0.01）。
CGXZ 丸通过调节 p-JNK、p-c-Jun、caspase-8、Fas 和 Fas-L 的表达，抑制肝细胞凋亡的发生，从而发挥对 NASH 的治疗作用。
