[关键词]
[摘要]
目的 研究刺蒺藜超微粉通过瘦素介导的JAK2/STAT3通路对肥胖性高血压大鼠肾脏影响的机制。方法 由高脂饮食诱导肥胖性高血压大鼠模型,随机分为替米沙坦组(8只,3.4 mg/kg),刺蒺藜组(8只,17.2 mg/kg),模型组(8只,生理盐水2 mL/d),另设普通饲料喂养的10只大鼠为对照组(生理盐水2 mL/d),共给药12周,定期记录检测大鼠血压、体质量,实验结束时检测大鼠血脂水平,ELISA法检测大鼠血清血管紧张素II(Ang II)、β2微球蛋白(β2-MG)和瘦素(Lep)的水平,HE染色观察大鼠肾脏及脂肪组织的形态学变化,免疫组化法检测各组大鼠肾脏AT1和LepR水平;qRT-PCR法和Western blotting法检测大鼠肾脏JAK、STAT的mRNA和蛋白水平的改变。结果 经药物干预12周后,各组肥胖性高血压大鼠血清循环AngII、β2-MG和Lep水平显著下降(P<0.05),免疫组化显示,与模型组比较,刺蒺藜组肾脏LepR1蛋白分布密度显著增加(P<0.05)。RT-PCR及Western blotting显示,与模型组比较,刺蒺藜组肾脏的JAK、STAT的mRNA和蛋白表达降低(P<0.05)。结论 刺蒺藜通过调控瘦素介导的JAK2/STAT3通路,改善瘦素抵抗,治疗肥胖性高血压。
[Key word]
[Abstract]
Objective To observe the effect and explore the mechanism of Tribulus terrestris (TT) on kidney of rats with obesity-related hypertension through leptin mediated JAK2/STAT3 pathway. Methods To establish the model of rats with obesity-related hypertension by high-fat diet. The model rats were randomly divided into three groups:TT group (eight rats, 17.2 g/kg), Telmisartan group (eight rats, 3.4 mg/kg), and model group (eight rats, normal saline 2 mL/d). Rats were ig given drugs or saline for 12 weeks. The body weights and blood pressure were measured regularly. At the end of the study, the rats were sacrificed and the levels of serum lipid and angiotensinII (AngII) and β2-microglobulin (β2-MG) were determined by ELISA. Morphological changes of adipose tissue and kidney were observed by HE staining. The density of LepR in kidney was observed by immunohistochemical staining. Levels of mRNA and protein expression of JAK2 and STAT3 in kidney were determined by quantitive real-time PCR (qRT-PCR) and Western blotting. Results Both body weights and blood pressure of TT group were decreased (P<0.05). The levels of serum TG, TC, and LDL-C of TT group were decreased significantly (P<0.05). Kidney morphology of TT group was improved obviously and the size of lipocyte decreased. The levels of serum Ang II, Lep, and β2-MG of TT group decreased significantly (P<0.05). The density of LepR in kidney of TT group decreased significantly (P<0.05). The mRNA and protein expression of JAK2 and STAT3 in kidney of TT group was decreased significantly (P<0.05). Conclusion TT improves the leptin resistance of the obesity-related hypertensive rats mainly through JAK2/STAT3 pathway.
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[基金项目]
泰山学者岗位建设资金资助(#2012-55);山东省科技发展计划项目(2014GSF119011);山东省自然科学基金自主(ZR2014HL096)