目的 评价复方高滋斑片（Compound gaoziban tablet，CGT）对自发性高血压大鼠（Spontaneously hypertensive rats，SHR）的降压药效并探讨其对RAAS（Renin-angiotensin-aldosterone system）调控的机制研究。方法 将40只12周龄的SHR随机分为：模型组、阳性药组（酒石酸美洛托尔片组）、复方高滋斑片高、中、低剂量组；另设对照组为8只同周龄的Wistar-Kyoto大鼠（WKY）。每天以10 mL·kg^-1的灌胃体积，连续口服给药9周，并每周定时测量大鼠收缩压（Systolic pressure，SBP）。给药9周后处死各组大鼠并取材，检测血清血脂水平、肝功能水平，用ELISA法检测肾素（Renin）、血管紧张素Ⅱ（AngiotensinⅡ，AngⅡ）、醛固酮（Aldosterone，ALD）、内皮素1（Endothelin-1，ET-1）的水平；通过HE染色和Masson染色观察大鼠脏器组织的病理变化。qRT-PCR法检测血管紧张素转化酶（Angiotensin-converting enzyme，ACE）、血管紧张素Ⅱ1型受体（Angiotensin Ⅱ type 1 receptor，AT1R）和内皮型一氧化氮合成酶（Endothelial nitric oxide synthase，eNOS）的相对表达量。结果 与模型组相比，CGT对收缩压均有一定程度的降低（P < 0.05）。检测血清中血脂水平，发现与模型组比较，CGT对大鼠血清中的甘油三酯（Triglyceride，TG）和高密度脂蛋白胆固醇（High density lipoprotein cholesterol，HDL-C）的水平有显著性的降低作用（P > 0.05），但对大鼠血清中的葡萄糖（Glucose，Glu）、总胆固醇（Total cholesterol，TC）和低密度脂蛋白胆固醇（Low density lipoprotein cholesterol，LDL-C）均无影响。检测血清样本中的转氨酶水平，发现与模型组比较，CGT对大鼠血清中的谷草转氨酶（Aspartate aminotransferase，AST）、谷丙转氨酶（Alanine aminotransferase，ALT）和谷胱甘肽S转移酶（Glutathione S-transferase，GST）的水平均有不同程度的降低作用（P < 0.05，P < 0.01）。检测血清样本中Renin、AngⅡ、ALD、ET-1的含量，与模型组比较，CGT对大鼠血清中的Renin、AngⅡ、ALD和ET-1的含量均有不同程度的降低（P < 0.05，P < 0.01）。qRT-PCR结果显示CGT能显著下调ACE、AT1R mRNA的表达（P < 0.05，P < 0.01），显著上调eNOS mRNA的表达（P < 0.05，P < 0.01）。结论 复方高滋斑片具有一定的降压效果，且对高血压引发的肝脏和肾脏的病变具有一定的缓解作用；其降压机制可能与调节RAAS有关。

Objective To evaluate the antihypertensive effect of Compound gaoziban tablet (CGT) on Spontaneous hypertensive rats (SHR) and to discuss the related mechanisms.Methods Forty 12-week-old SHR rats were taken as the disease model animal study object and randomly divided into five groups, including disease model group, positive drug (Metoprolol tartrate tablet) group, CGT high dose group, CGT middle dose group and CGT low dose group. Then, eight Wistar-Kyoto (WKY) rats were taken as normal control group. The drug/distilled water (10 mL·kg^-1) were orally administered continuously for 9 weeks. Systolic blood pressure was measured at the same time point weekly. After 9 weeks, serum lipid levels and transaminase levels were evaluated. The level of Renin (Renin), Angiotensin Ⅱ (AngⅡ), Aldosterone (ALD) and Endothelin 1 (ET-1) were analyzed via ELISA. The pathological changes of organ tissues were observed by Hematoxylin-eosin (HE) staining and Masson staining. qRT-PCR method was used for detection of mRNA relative expression of Angiotensin converting enzyme (ACE), Angiotensin Ⅱ type 1 receptor (AT1R) and Endothelial nitric oxide synthase (eNOS).Results Compared with the model group, CGT has a certain lowering effect on systolic blood pressure (P < 0.05). Based on serum samples analyzing results, CGT had a significant lowering effect on the level of Triglyceride (TG) and the level of High density lipoprotein cholesterol (HDL-C) in serum samples of rats (P > 0.05), but had no effect on the level of Glucose (Glu), Total cholesterol (TC) and Low density lipoprotein cholesterol (LDL-C). Transaminase levels in serum samples were also evaluated. Compared with the model group, CGT had a different lowering effect on the level of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Glutathione S-transferase (GST) in serum samples of rats (P < 0.05, P < 0.01). The serum samples were also tested for the content evaluation of Renin, AngⅡ, ALD and ET-1. Compared with the model group, the content of Renin, AngⅡ, ALD and ET-1 in each group have different low degrees (P < 0.05, P < 0.01). The Masson staining results of the kidney tissue of rats in all groups were statistically analyzed, and CGT can significantly reduce the collagen production in rat kidney (P < 0.05). qRT-PCR results showed that CGT significantly down-regulated the expression levels of ACE and AT1R mRNA (P < 0.05, P < 0.01) and upregulated the expression of eNOS mRNA (P < 0.05, P < 0.01).Conclusion CGT has antihypertensive effect and it can alleviate the disease to some extent on liver and kidney pathological changes caused by hypertension. Its antihypertensive mechanism may be related to the regulation of Renin-Angiotensin-Aldosterone system (RAAS).

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国家科学技术部国家科技重大专项课题（2017ZX09301045）：民族药新品种研发及其关键创新技术，负责人：尹海龙。