右归丸对肾阳虚高脂血症大鼠JAK/STATs通路的实验探讨

Experimental Study of Yougui Wan on JAK/STATs Pathway in Kidney-yang Deficiency and Hyperlipidemia Rats

目的:通过大剂量肌注氢化可的松复制肾阳虚高脂血症大鼠模型,并给予右归丸干预,观察右归丸对于模型大鼠酪氨酸蛋白激酶2(JAK2),信号转导子和转录激活子3(STAT3)和肝X受体α(LXRα)蛋白和基因表达的影响,探讨JAK2/STAT3信号转导通路与肾阳虚大鼠血脂异常的相关性。方法:SD大鼠60只分为正常组、模型组、右归丸组(2.43 g·kg-1),利用大剂量im氢化可的松制作肾阳虚大鼠模型,正常组不造模,模型组造模并给予生理盐水,右归丸组造模给予右归丸混悬液ig,检测血清脂类物质甘油三脂(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)含量,免疫组化检测肝组织LXRα蛋白表达,RT-PCR检测实验大鼠肝组织JAK2,STAT3和LXRα基因的表达。结果:与正常组比较,模型组大鼠血清中TG,TC,LDL-C含量显著升高(P<0.01),HDL-C含量显著降低(P<0.01);与模型组比较,右归丸组大鼠血清中TG,TC,LDL-C含量显著下降(P<0.01),HDL-C含量显著升高(P<0.01)。与正常组比较,模型组肾阳虚高脂血症大鼠肝内LXRα蛋白表达明显增加(P<0.05),JAK2,STAT3和LXRα基因表达增加(P<0.05);与模型组比较,右归丸组大鼠肝内LXRα蛋白表达明显减少(P<0.05),JAK2,STAT3和LXRα基因表达减少(P<0.05)。结论:肌注氢化可的松制造的肾阳虚高脂血症模型可能是通过上调了JAK2/STAT3信号转导通路中的JAK2,STAT3和LXRα蛋白和基因而影响了血液中甘油三酯和胆固醇的代谢,右归丸可能通过抑制JAK2/STAT3信号转导通路中相关细胞因子蛋白和基因的表达来降低模型大鼠血液中脂类的含量。

Objective： To establish kidney-yang deficiency and hyperlipidemia rat models through high dose of hydrocortisone injection,with intervention by Yougui Wan,observe the effects of Yougui Wan on janus activated kinase signaltransducer 2（ JAK2）,signal transducer and activator of transcription 3（ STAT3） and liver X receptor α（ LXRα） protein and gene expression in model rats,and to study the relationship between JAK2 / STAT3 signal transduction pathway and blood lipid abnormality of kidney-yang deficiency rats. Method： Sixty SD rats were divided into normal group,model group,Yougui Wan group（ 2. 43 g·kg- 1）. Kidney-yang deficiency rat models were made using high dose hydrocortisone injections. Normal control rats were not modeled. The rats in model group were modeled and received normal saline. Rats in Yougui Wan group were modeled and received Yougui Wan suspension ig. Triglycerides（ TG）,total cholesterol（ TC）,low-density lipoprotein cholesterol（ LDLC）,and high density lipoprotein cholesterol（ HDL-C） contents were detected. Immunohistochemitry was done to detect LXRα protein expression in liver tissues,and RT-PCR was used to detect the expressions of JAK2,STAT3 and LXRα in rat liver tissues. Result： Compared with the normal control group,the contents of TG,TC,LDL-C in serum of model group and Yougui Wan group rats were increased significantly（ P〈0. 01）,HDL-C content was significantly decreased（ P〈0. 01）. Compared with the model group,the contents of TG,TC,LDL-C in serum of Yougui Wan group were decreased significantly（ P〈0. 01）,and HDL-C content was significantly increased（ P〈0. 01）. Compared with normal control group,the expression of LXRα protein in kidney-yang deficiency rats of model group was significantly increased（ P〈0. 05） in the liver,and JAK2,STAT3 and LXRα gene expressions were increased（ P〈0. 05）. Compared with the model group,the expression of LXRα protein in rat liver of Yougui Wan group was significantly decreased（ P〈0. 05）,and JAK2,STAT3 and LXRα gene expressions were decreased（ P〈0. 05）. Conclusion： The kidney-yang deficiency and hyperlipidemia rat models made by hydrocortisone intramuscular injections may affect blood triglycerides and cholesterol metabolism through up-regulating JAK2,STAT3 and LXRα proteins and genes in pathways transduced by JAK2 / STAT3 signals. Yougui Wan may reduce the content of lipid in model rats by inhibiting expression of related cytokines proteins and genes in pathways transduced by JAK2 / STAT3 signals.