半夏白术天麻汤改善肥胖性高血压大鼠肾脏损害的机制研究

Mechanism of Banxia Baizhu Tianma Decoction on Renal Protection of Obesity-Related Hypertensive Rats

目的:观察半夏白术天麻汤通过对肥胖性高血压大鼠肾脏脂肪酸转运酶/B类清道夫受体CD36(CD36)表达的调节,探讨明确其在肥胖性高血压病理进程中肾脏保护的药理机制。方法:高脂饲料喂养wistar大鼠25周诱导肥胖性高血压大鼠模型,分为半夏白术天麻汤高剂量组[13.8 g/(kg·d)]、半夏白术天麻汤低剂量组[6.9 g/(kg·d)]、替米沙坦组(6.3g/kg/d,西药对照)和模型组,各药物灌胃12周,测量大鼠体质量、血压、血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)含量,ELISA法检测血清中血管紧张素Ⅱ(AngⅡ)、内皮素1(ET-1)、可溶性CD36、β2微球蛋白(β2-MG)的含量;HE染色、透射电镜(TEM)观察大鼠肾脏病理改变;实时荧光定量PCR(q-PCR)和Western blotting(WB)法分别检测肾脏CD36、核因子κB(NF-κB)、转化生长因子β1(TGF-β1)的mRNA和蛋白质表达。结果:肥胖性高血压模型组大鼠体质量、血压升高,血清TC、LDL-C升高(P<0.05),血清AngⅡ、ET-1、可溶性CD36、β2-MG显著升高(P<0.05);用药12周后,大鼠血压、体质量均有不同程度的下降,血清TC、TG、LDL-C、AngⅡ、ET-1、可溶性CD36、β2-MG降低(P<0.05),HDL-C升高。模型组大鼠肾脏形态结构异常、CD36分布增加;各药物组肾脏形态明显改善、CD36分布减少。q-PCR和WB显示模型组大鼠肾脏CD36、NF-κB、TGF-β1的mRNA和蛋白质表达均显著增加,半夏白术天麻汤和/或替米沙坦干预后CD36、NF-κB、TGF-β1的mRNA和蛋白质表达均显著下降。结论:半夏白术天麻汤在肥胖性高血压病理进程中具有明确的肾脏保护功效,CD36是其有效改善肥胖性高血压肾脏损伤的靶点之一。

Objective： To observe the effect of Banxia Baizhu Tianma Decoction （BBT） on the expression of renal fatty acid translocase/scavenger receptor class B （ CD36 ） and explore the pharmacological mechanism of renal protection of BBT on obesity - related hypertensive rats. Methods ： Wistar rats were fed with high fat diet for 25 weeks to induce the o- besity -related hypertensive models which were divided into four groups：BBT high dose group [ 13.8 g/（ kg · d） ], BBT low dose group [ 6.9 g/（ kg · d） ] ,telmisartan group [ 6.3 g/（ kg · d） ] and the model group. Drugs were intragastrically administrated to rats for 12 weeks. Body weight, blood pressure, serum triglyceride （ TG）, total cholesterol （ TC）, low den- sity lipoprotein （ LDL - C） and high density lipoprotein （ HDL - C） were monitored. The levels of angiotensin II （ Ang II） ,endothelin 1 （ET- 1 ） ,soluble CD36 and beta 2 microglobulin （132 -MG） were measured by ELISA. Renal patho- logical changes were Observed by HE staining and transmission electron microscopy （TEM）. The mRNA and protein ex- pressions of renal CD36 ,nuclear factor kappa B （ NF - kB） and transforming growth factor beta 1 （ TGF - β1 ） were as- sayed by real- time fluorescence quantitative PCR （q- PCR） and western blotting （WB）. Results： Body weight,blood pressure, serum TC, LDL - C, Ang II, CD36, ET - 1 and β2 - MG were increased in model group rats. After drug adminis- tration, body weight, blood pressure, blood lipid, Ang II, CD36, ET - 1 and β2 - MG were decreased （ P 〈 0.05 ）. The re- nal morphology and structure were abnormal and the distribution of CD36 was increased in model group. The renal mor- phology of the drug groups was significantly improved and the distribution of CD36 decreased. Q - PCR and WB showed that the mRNA and protein expressions of renal CD36, NF - KB and TGF - β1 were significantly increased in model group rats. While BBT down- regulated the mRNA and protein expressions of CD36, NF- KB and TGF-β1. Conclusion： Banxia Baizhu Tianma Decoction demonstrated the Significant renal protective effect in the pathological process obesity - related hypertension. CD36 may be one of the target of BBT.