肝复健方对瘦素调控肝纤维化大鼠JAK2/STAT3信号通路的影响

Effect of Ganfujian Formula on the JAK2/STAT3 Signaling Pathway in Leptin-Induced Liver Fibrosis in Rats

目的探讨肝复健方抗肝纤维化(HF)的可能作用机制。方法将60只SD大鼠随机分为正常组、模型组、肝复健方低剂量组、肝复健方中剂量组、肝复健方高剂量组、秋水仙碱组各10只,除正常组外其余各组腹腔注射猪血清0.5ml/只制备HF模型,每周2次,共8周。造模成功后,肝复健方低、中、高剂量组分别给予含1.4g/ml、2.8g/ml、4.2g/ml肝复健方水煎剂灌胃;秋水仙碱组给予秋水仙碱片混悬液0.154mg/kg;正常组和模型组给予10ml/kg生理盐水灌胃。RT-PCR法检测瘦素(Leptin)及Leptin受体(OB-Rb)mRNA的表达,Western blot法检测酪氨酸蛋白激酶2(JAK2)、信号转导和转录激活蛋白3(STAT3)的表达。结果与正常组比较,其余各组大鼠Leptin mRNA、OB-Rb mRNA、JAK2、STAT3表达明显增强(P<0.05);肝复健方低、中、高剂量组和秋水仙碱组较模型组大鼠上述各项指标明显降低(P<0.05),并且肝复健方高剂量组较肝复健方中、低剂量组和秋水仙碱组降低明显(P<0.05)。结论肝复健方抗HF的作用可能与其抑制Leptin、OB-Rb表达,进而抑制JAK2/STAT3信号通路有关。

Objective To research the possible mechanism of Ganfujian Formula （formula for liver recovery） for liver fibro- sis. Methods The SD rats were randomized into the normal group, model group, Ganfujian Formula low-dose group, Ganfu- jian Formula middle-dose group, Ganfujian Formula high-dose group and eolchicines group, with 10 in each. The liver fibrosis model was established with intraperitoneal injection of 0.5 ml pig serum twice weekly for 8 weeks in each group except the nor- mal group. Both the normal and model groups were gavaged with 10 ml/kg normal saline respectively. The Ganfujian Formula low-dose, middle-dose and high-dose groups were garaged with 1.4 g/ml, 2.8 g/ml and 4.2 g/ml Ganfujian Formula decoction respectively. The colchicine group was given 0. 154 mg/kg suspension liquid of colchieine tablets. The expressions of leptin mRNA and leptin receptor （OB-Rb） mRNA were detected with reverse transcription-polymerase chain reaction. The expres- sions of Janus kinase 2 （JAK-2） and signal transducer and activator of transcription S （STAT3） were detected with Western blot. Results Comparing with the normal group, the expressions of leptin mRNA, OB-Rb mRNA, JAK2 and STAT3 were significantly increased in other groups （P〈0. 05）. Comparing with the model group, the expressions of leptin mRNA, OIA-Rb mRNA, JAK2 and STAT3 were significantly decreased in the Ganfujian Formula low-dose, middle-dose and high-dose groups and colchicine group （P〈0.05）, especially in the Ganfujian Formula high-dose group （P〈0.05）. Conclusion The possible mechanism of Ganfujian Formula for liver fibrosis is inhibiting the expressions of leptin and OB-Rb and thereby inhibiting JAK2/STAT3 signaling pathway.