黄连吴茱萸组分配伍对高脂血症大鼠JAK2/STAT3通路的影响

Effects of Drug Combination of Huanglian (Rhizoma Coptidis) and Wuzhuyu (Evodia Rutaecarpa) on JAK2/STAT3 Pathway in Hyperlipidemia Rats

目的通过考察黄连吴茱萸组分配伍对高脂血症模型大鼠血清瘦素(Leptin)、肝脏组织中瘦素受体(Ob-Rb)、酪氨酸蛋白激酶2(JAK2)、信号转导子和转录激活子3(STAT3)表达的影响,探讨其对高脂血症大鼠JAK2/STAT3信号转导通路的影响。方法建立SD大鼠高脂血症模型,将造模成功的大鼠随机分为模型对照组、辛伐他汀组(7mg/kg)、黄连吴茱萸组分配伍中剂量组(44.6mg/kg)、黄连吴茱萸组分配伍高剂量组(89.1mg/kg),除空白组外,其余各组继续采用高脂饲料喂养,连续灌胃给药8周,检测各组动物血清甘油三脂(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),及血清瘦素(Leptin)含量;HE染色检测各组肝脏病变程度;采用Western blot方法检测各组大鼠肝脏Ob-Rb、JAK2、及STAT3蛋白表达。结果黄连吴茱萸组分配伍能显著降低高脂血症模型大鼠血清TC、TG、LDL-C含量(P<0.05或P<0.01),升高HDL-C含量(P<0.05),改善模型对照组大鼠肝脏的纤维化病变,降低血清Leptin含量(P<0.01)。与模型对照组比较,黄连吴茱萸组分配伍干预后,高脂血症模型大鼠肝脏中Ob-Rb、JAK2和STAT3表达升高(P<0.05或P<0.01)。结论黄连吴茱萸配伍能有效改善高脂模型大鼠血脂水平,其可能通过调节JAK2/STAT3信号转导通路实现。

Objective To illustrate effects of drug combination of Huanglian and Wuzhuyu on JAK2/STAT3 signal transduction pathway from serum leptin,hepatic janus activated kinase signal transducer 2（ JAK2）,signal transducer and activator of transcription 3（ STAT3） and leptin receptor protein expressions in hyperlipidemia rats. Methods After establishing the hyperlipidemic model successfully,SD rats were divided into normal group,model group,simvastatin group（ 7mg · kg-1）,Huanglian Wuzhuyu middle dosage group（ 44. 6 mg·kg-1）,and Huanglian Wuzhuyu high dosage group（ 89. 1 mg·kg-1）. The model rats of hyperlipidemia were fed with high fat diet,while normal control rats were fed with fundamental diet. After 8 weeks treatment,serum triglycerides（ TG）,total cholesterol（ TC）,low-density lipoprotein cholesterol（ LDL-C）,high density lipoprotein cholesterol（ HDL-C）,and leptin content in serum of rats were detected. HE staining was conducted to detect steatosis in liver tissues,and RT-PCR was used to detect the expressions of JAK2,STAT3 and leptin receptor（ Ob-Rb） in rat liver tissues. Western blotting were employed to detect P-JAK2,P-STAT3,and Ob-Rb expression levels in the liver respectively. Results The results showed that component compatibility of Huanglian and Wuzhuyu significantly decreased the TG,TC,LDL-C content in serum of the hyperlipidemic rats（ P〈0. 05）,while elevating serum HDL-C content in hyperlipidemic rats as well（ P〈0. 05 or P〈0. 01）,ameliorating steatosis in liver,decreasing leptin level in serum,and enhanced the expression of leptin receptor m RNA and P-JAK2/P-STAT3 and Ob-Rb levels（ P〈0. 05 or P〈0. 05）. Conclusion Component compatibility of Huanglian and Wuzhuyu can regulate the metabolic process of blood lipid levels of hyperlipidemia model rats,which might be contributed to its effect on JAK2/STAT3 pathways.