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目的通过观察研究补阳还五汤对高血压前期Dahl盐敏感大鼠NO/cGMP/PKG信号转导通路的影响,探讨其对高血压前期肾脏损害的保护机制。方法选择7周龄盐抵抗大鼠20只,随机分为正常组和正常给药组;盐敏感大鼠20只,随机分为模型组和模型给药组。在SPF动物实验中心适应性喂养1周,用8%NaCl高盐饲料喂食12 d。采用智能无创血压计监控大鼠血压,在12 d后模型组大鼠血压值升至120~139/80~89mm Hg(1 kPa=7.5 mm Hg),确定为高血压前期大鼠模型。停止高盐喂饲,改为普通饲料喂养,并进行补阳还五汤灌胃治疗。治疗结束后进行大鼠腹主动脉取血,检测血清尿素氮(UREA)、血肌酐(CREA)、血尿酸(UA);取大鼠左肾组织,Elisa法检测NO含量表达,荧光定量PCR法检测溶解型鸟苷酸环化酶(sGC)、蛋白激酶G(PKG)的mRNA表达;大鼠肾组织行HE染色,观测肾组织形态学变化。结果与模型组比较,补阳还五汤组UREA、CREA、UA含量显著降低(P<0.05),NO含量明显升高(P<0.05),sGC、PKG的mRNA表达显著升高(P<0.05)。HE染色结果显示,补阳还五汤组大鼠肾组织形态较模型组明显改善。结论补阳还五汤可用于保护高血压前期肾脏功能,防止肾脏并发症的发生,其机制可能与激活NO/cGMP/PKG信号转导通路有关。
Objective To observe the effect of Buyang Huanwu decoction on NO / cGMP / PKG signal transduction pathway in prehypertensive Dahl salt-sensitive rats, and to explore its protective mechanism on prehypertensive renal damage. Methods Twenty saline-resistant rats at 7 weeks of age were randomly divided into normal group and normal group. Twenty saline-sensitized rats were randomly divided into model group and model group. Adaptive feeding in SPF Animal Experimental Center for 1 week, feeding with 8% NaCl high salt diet for 12 days. The blood pressure was monitored by a smart noninvasive sphygmomanometer. After 12 days, the blood pressure of the model group increased to 120 ~ 139/80 ~ 89 mm Hg (1 kPa = 7.5 mm Hg), which was determined as a prehypertensive rat model. Stop high-salt feed, feed instead of normal feed, and make up the yang huanwu decoction gavage treatment. Serum urea nitrogen (UREA), serum creatinine (CREA) and serum uric acid (UA) were measured in the abdominal aorta of the rats after the treatment. The left kidney of the rats was taken out and the expression of NO was detected by Elisa method. The mRNA expressions of soluble guanylate cyclase (sGC) and protein kinase G (PKG) were detected. The renal tissues of rats were stained with HE and the morphological changes of renal tissues were observed. Results Compared with model group, the content of UREA, CREA and UA in Buyanghuanwu Decoction group was significantly lower (P <0.05), the content of NO was significantly higher (P <0.05) and the mRNA expressions of sGC and PKG were significantly increased ). The results of HE staining showed that the morphology of kidney in Buyang Huanwu Decoction group was significantly improved compared with model group. Conclusion Buyang Huanwu decoction can be used to protect the renal function in prehypertension and prevent the occurrence of renal complications, which may be related to the activation of NO / cGMP / PKG signal transduction pathway.