通心络对血管紧张素Ⅱ致大鼠内皮损伤的保护作用

The protective effect of Tongxinluo to endothelium injured by angiotensin-II in vivo in rats

目的:观察中药通心络对血管紧张素Ⅱ致大鼠内皮损伤模型血管内皮的保护作用。方法:将54只SD大鼠随机分为血管紧张素Ⅱ(AngⅡ)组、通心络保护(TXL)组、对照(假手术)组,每组18只。每组分别于7、14、28d取材。AngⅡ组和TXL组分别于皮下埋置不同缓释终点的AngⅡ缓释泵,TXL组每天予以通心络(0.8g·kg-1·d-1)灌胃。测量颈总动脉血压,血浆AngⅡ、内皮素(ET-1)和6-酮-前列腺素F1α(6-Keto-PGF1α)含量,扫描电镜观察内皮的病理损伤,检测凋亡基因Bax、Bcl-2和烟酰胺腺嘌呤二核苷酸(NADPH)氧化酶亚基p22phox基因的表达。结果:3组血压都未升高,但AngⅡ组和TXL组的AngⅡ水平明显高于假手术组。电镜显示TXL组血管壁上内皮细胞的剥脱面积明显较同时间点AngⅡ组少。TXL组血浆ET-1在14d较AngⅡ组降低(P<0.05),6-Keto-PGF1α水平以及Bax和p22phox基因表达在14、28d与AngⅡ组明显不同(P<0.05),Bcl-2/Bax比值在7、14、28d3时间点上较AngⅡ组升高(P<0.05)。结论:通心络可以抑制NADPH氧化酶p22phox基因表达,抑制Bax基因表达,使Bcl-2/Bax比值明显增高,减少ET-1并增加6-Keto-PGF1α分泌,显示出对内皮损伤的保护作用。

Objective： To observe the protective effect of Tongxinluo on artery endothelium injured by angiotensin Ⅱ osmotic pump in rat. Methods： 54 SD rats were divided into sham group（18 rats）, angiotensin Ⅱ group（18 rats） and Tongxinluo group（18 rats）.There were three time points, 7d, 14d and 28d in each group. Angiotensin Ⅱ osmotic pump at the dose of 200ng· min^-1 ·kg^-1 were embedded in the rat back of angiotensin Ⅱ （Ang Ⅱ ） group and Tongxinluo （ TXL ） group.ln TXL group, Tongxinluo（0.8gng·kg^-1· d^-1） was given by gastric tube after Angiotensin Ⅱ pump were used. All animals were sacrificed in 7th, 14th and 28th day respectively. Blood pressure, Ang Ⅱ, ET-1, 6-Keto- PGF1α, Bax, Bcl-2 and p22phox mRNA were measured in different methods. Results： The plasma level of angiotensin Ⅱ in Ang Ⅱ group and TXL group was higher than the Sham group, meanwhile the blood pressure measured from carotid artery of the three groups was not high. Compared with Ang Ⅱ group, the blood level of 6-Keto-PGF1α, the Bax and NADPH p22phox mRNA significantly decreased in TXL group, especially in the time point of 14d and 28d. The marked difference of the level of ET-1 between Ang Ⅱ group and TXL group existed in the time point of 14d. The significant difference of Bcl-2/Bax between Ang Ⅱ group and TXL group existed in three time points. Conclusions： Tongxinluo could protect the endothelium against the injury from Angiotensin Ⅱ by inhibiting the expression of p22phox mRNA, Bax mRNA and Bcl-2 mRNA and reducing the blood level of ET-1 and 6-Keto-PGF1α.