天麻钩藤饮对肾性高血压动物模型的作用机制探讨

Mechanism of action of Tianma Gouteng decoction on animal models of renal hypertension

目的:探讨中药复方天麻钩藤饮治疗肾性高血压动物模型的疗效及可能的作用机制。方法:选取造模成功的肾性高血压SD大鼠24只,将其随机分为模型组、中药组、西药组,每组各8只,另以正常同周龄的SD大鼠作为空白组。中药组予中药复方天麻钩藤饮灌服,西药组予雷米普利灌服,空白组和模型组灌服同体积的纯净水,共干预4周。分别于手术前后、给药后每周测定尾动脉血压,于给药4周后检测血清血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)水平,主动脉、血管紧张素Ⅱ1型受体(AT1R)、血管紧张素转化酶(ACE)、内皮型一氧化氮合酶(eNOS)、内皮素(ET)的mRNA相对表达量,动脉B细胞淋巴瘤因子-2相关X蛋白(Bax)、含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)蛋白表达量。结果:与空白组比较,其余3组在结扎肾动脉手术后收缩压均明显升高,差异均有统计学意义(P<0.01),说明动物模型分配合理。给药后中药组、西药组的收缩压每周均明显降低,与模型组比较,差异均有统计学意义(P<0.01)。给药4周后,与空白组比较,模型组大鼠的AngⅡ、ALD水平明显升高,AT1R、ACE、ET的mRNA相对表达量明显上调,eNOS的mRNA相对表达量明显下调,Bax、Caspase-3蛋白表达量量显著增加,差异均有统计学意义(均P<0.01)。与模型组比较,中药组、西药组大鼠的AngⅡ、ALD水平明显降低,ACE、ET的mRNA相对表达量明显下调,eNOS mRNA相对表达量上调,Bax蛋白表达量降低,差异均有统计学意义(P<0.01);中药组AT1R的mRNA相对表达量、Caspase-3蛋白表达与模型组比较,差异有统计学意义(P<0.01)。结论:天麻钩藤饮能通过调控肾素-血管紧张素-醛固酮系统(RAAS)和内皮素-一氧化氮系统(ET-NO)降低血压,同时也可抑制血管内皮细胞的凋亡,缓解血管重构的病理进程。

Objective: To investigate the therapeutic effect of the traditional Chinese medicine compound Tianma Gouteng decoction on animal models of renal hypertension and its possible mechanism of action.Methods: After successful modeling, a total of 24 Sprague-Dawley rats with renal hypertension were randomly divided into model group, traditional Chinese medicine group, and Western medicine group, with 8 rats in each group, and normal Sprague-Dawley rats with the same age in weeks were selected as blank group.The rats in the traditional Chinese medicine group were given compound Tianma Gouteng decoction by gavage, those in the Western medicine group were given Ramipril by gavage, and those in the blank group and the model group were given an equal volume of purified water.Intervention was given for 4 weeks.Caudal arterial blood pressure was measured before and after surgery and each week after administration;the relative mRNA expression levels of angiotensin II(AngII),aldosterone(ALD),angiotensin II type 1 receptor(AT1 R),angiotensin-converting enzyme(ACE),endothelial nitric oxide synthase(eNOS),and endothelin(ET) and the protein expression levels of Bcl-2 related X gene(Bax) and caspase-3 in blood were measured after 4 weeks of administration.Results: Compared with the blank group, the other three groups had a significant increase in systolic pressure after ligation of renal artery(P<0.01),suggesting that the animal models were assigned reasonably.Compared with the model group, the traditional Chinese medicine group and the Western medicine group had a significant reduction in systolic pressure each week after administration(P<0.01).Compared with the blank group after 4 weeks of administration, the model group had significant increases in the levels of AngII and ALD,significant upregulation of the relative mRNA expression levels of AT1 R,ACE,and ET,significant downregulation of the relative mRNA expression level of eNOS,and significant increases in the protein expression levels of Bax and caspase-3(all P<0.01).Compared with the model group, the traditional Chinese medicine group and the Western medicine group had significant reductions in the levels of AngII and ALD,significant downregulation of the relative mRNA expression levels of ACE and ET,significant upregulation of the relative mRNA expression level of eNOS,and a significant reduction in the protein expression level of Bax(P<0.01),and there were significant differences in the relative mRNA expression level of AT1 R and the protein expression level of caspase-3 between the traditional Chinese medicine group and the model group(P<0.01).Conclusion: Tianma Gouteng decoction can reduce blood pressure by regulating the renin-angiotensin-aldosterone system and the endothelin-nitric oxide system, inhibit the apoptosis of vascular endothelial cells, and alleviate the pathological process of vascular remodeling.