拉西地平对自发性高血压大鼠模型血管内皮的保护作用及机制分析
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摘要
目的探讨拉西地平对自发性高血压大鼠模型血管内皮功能的保护作用,并分析其可能的作用机制。方法选取50只Wistar大鼠为WKY组,分为WKY对照组和WKY研究组,每组25只;50只自发性高血压大鼠为SHR组,分为SHR对照组和SHR研究组,每组25只。WKY研究组和SHR研究组大鼠给予拉西地平,WKY对照组和SHR对照组大鼠给予等体积的生理盐水,持续8周。各组大鼠分别于干预前后测量尾动脉收缩压。采用肠系膜上动脉血管舒张试验检测肠系膜动脉舒张度,Western blot检测主动脉Cx37蛋白表达水平,硝酸还原法检测血清NO水平,ELISA检测血浆ET水平及血清TNF-α水平。结果 SHR研究组和SHR对照组大鼠平均动脉压明显高于WKY研究组和WKY对照组(P<0.05);与干预前比较,干预后的SHR研究组大鼠平均动脉压明显降低,且明显低于SHR对照组,差异有统计学意义(P<0.05)。与WKY研究组和WKY对照组相比较,SHR研究组和SHR对照组大鼠肠系膜上动脉舒张度、主动脉Cx37蛋白表达水平、血清NO水平明显降低(P<0.05),而SHR研究组明显高于SHR对照组(P<0.05);血浆ET水平、血清TNF-α水平明显升高(P<0.05),而SHR研究组明显低于SHR对照组(P<0.05)。结论拉西地平能够改善血管内皮功能,其可能通过调节血管舒张因子NO、收缩因子ET的表达,保证细胞间缝隙连接通讯正常,抑制炎症反应,从而保护血管内皮。
Objective To discuss the protective effect and possible mechanism of lacidipine on vascular endothelium in spontaneously hypertensive rat model.Methods Fifty Wistar rats were selected as the WKY group and divided into the WKY control group and WKY research group,25 cases in each group;fifty spontaneous hypertensive rats were selected as the SHR group and divided into the SHR control group and SHR research group,25 cases in each group.The WKY research group and SHR research group were given lashidipine,and the WKY control group and SHR control group were given the same volume of normal saline solution for continuous 8 weeks.The systolic pressure of tail artery in each group was measured before and after intervention.The mesenteric artery diastolic degree was detected by adopting the tmesenteric superior artery diastolic test,the aortic Cx37 protein expression level was detected by Western blot method,the serum NO level was detected by using the nitrate reduction method,the plasma ET and serum TNF-αlevels were detected by using ELISA method.Results The mean arterial pressure in the SHR research group and SHR control group were significantly higher than that in the WKY research group and WKY control group(P<0.05);compared with before intervention,the mean arterial pressure after intervention in the SHR research group was significantly decreased,moreover significantly lower than that in the SHR control group,and the difference was statistically significant(P<0.05).Compared with the SKY research group and WKY control group,the diastolic degree of mesenteric superior artery,expression levels of aortic Cx37 protein and serum NO levels in the SHR research group and SHR control group were significantly decreased(P<0.05),while the SHR research group was significantly higher than the SHR control group(P<0.05);plasma ET level and serum TNF-αlevel were significantly increased(P<0.05),while the SHR research group was significantly lower than the SHR control group(P<0.05).Conclusion Lacidipine can effectively reduce the mean arterial pressure in spontaneously hypertensive rats,and improve it′s endothelial function,ensure the normality of the intercellular gap junction communications possibly by adjusting the expression of vasodilatation factor NO and contraction factor ET,inhibit the inflammatory response,thus protect the vascular endothelial function.
Objective To discuss the protective effect and possible mechanism of lacidipine on vascular endothelium in spontaneously hypertensive rat model.Methods Fifty Wistar rats were selected as the WKY group and divided into the WKY control group and WKY research group,25 cases in each group;fifty spontaneous hypertensive rats were selected as the SHR group and divided into the SHR control group and SHR research group,25 cases in each group.The WKY research group and SHR research group were given lashidipine,and the WKY control group and SHR control group were given the same volume of normal saline solution for continuous 8 weeks.The systolic pressure of tail artery in each group was measured before and after intervention.The mesenteric artery diastolic degree was detected by adopting the tmesenteric superior artery diastolic test,the aortic Cx37 protein expression level was detected by Western blot method,the serum NO level was detected by using the nitrate reduction method,the plasma ET and serum TNF-αlevels were detected by using ELISA method.Results The mean arterial pressure in the SHR research group and SHR control group were significantly higher than that in the WKY research group and WKY control group(P<0.05);compared with before intervention,the mean arterial pressure after intervention in the SHR research group was significantly decreased,moreover significantly lower than that in the SHR control group,and the difference was statistically significant(P<0.05).Compared with the SKY research group and WKY control group,the diastolic degree of mesenteric superior artery,expression levels of aortic Cx37 protein and serum NO levels in the SHR research group and SHR control group were significantly decreased(P<0.05),while the SHR research group was significantly higher than the SHR control group(P<0.05);plasma ET level and serum TNF-αlevel were significantly increased(P<0.05),while the SHR research group was significantly lower than the SHR control group(P<0.05).Conclusion Lacidipine can effectively reduce the mean arterial pressure in spontaneously hypertensive rats,and improve it′s endothelial function,ensure the normality of the intercellular gap junction communications possibly by adjusting the expression of vasodilatation factor NO and contraction factor ET,inhibit the inflammatory response,thus protect the vascular endothelial function.
引文
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[13]肖艳,陈明.血管内皮功能检测[J].中华高血压杂志,2016,24(9):883-887.
[14]周锐.高血压患者血清肝细胞生长因子的表达及与血管内皮功能的关系[J].中国老年学杂志,2017,37(9):2181-2182.
[15]马少雯,柳俊,梁润和,等.药物治疗对高血压及高血压并发冠心病患者肱动脉内皮依赖性舒张功能的影响[J].岭南心血管病杂志,2017,23(2):197-200,214.
[16]牛俊红,张静,周永安.间隙连接蛋白40基因多态性与原发性高血压病的相关性研究[J].中西医结合心脑血管病杂志,2014,12(5):548-550.
[17]LI X,DAI Y N,YAN S J,et al.Resveratrol lowers blood pressure in spontaneously hypertensive rats via calciumdependent endothelial NO production[J].Clin Exp Hypertens,2016,38(3):287-293.
[2]车晓宁,阮彩莲.不同级别高血压患者胰岛素抵抗、血清脂联素水平的相关性[J].中国老年学杂志,2016,36(3):711-712.
[3]胡丽华,黄晓,蔡华秀,等.江西省城乡居民高血压患病现状调查及影响因素分析[J].中华高血压杂志,2017,25(2):169-175.
[4]李正欢,张晓云.高血压动物模型应用概况与研究进展[J].中华高血压杂志,2017,25(8):727-732.
[5]魏淑琴,樊金焱,刘玉玲,等.青岛市正常高值血压及高血压人群现况和全身血管损伤情况[J].中国老年学杂志,2017,37(16):4108-4110.
[6]栗源,可燕,蒋嘉烨,等.天麻钩藤饮对自发性高血压大鼠血管功能及肾脏蛋白表达的影响[J].中国中西医结合杂志,2015,35(4):481-487.
[7]LEMKENS P,SPIJKERS L J,MEENS M J,et al.Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR[J].Hypert Res,2017,40(8):738-745.
[8]CHIBIREVA M D,AFLYATUMOVA G N,MATVEEVA V,et al.Nitrogen oxide,endothelin-1,and serotonin in the blood of immature spontaneously hypertensive rats[J].Bull Exp Biol Med,2017,162(3):310-312.
[9]赵钐妤,王斌.血管相关疾病中缝隙连接的研究进展[J].医学信息,2017,30(11):12-14.
[10]阮承超,高平进.免疫与炎症参与高血压发生发展的机制探讨[J].中华高血压杂志,2017,25(4):319-321.
[11]范泸韵,张慧敏,杨丽睿,等.拉西地平分散片与苯磺酸氨氯地平治疗老年轻、中度原发性高血压的对比研究[J].中国循环杂志,2017,32(z1):215.
[12]潘伟健,郭颖秀,姚达安.拉西地平与硝苯地平治疗高血压的疗效对比观察[J].北方药学,2017,14(8):51-52.
[13]肖艳,陈明.血管内皮功能检测[J].中华高血压杂志,2016,24(9):883-887.
[14]周锐.高血压患者血清肝细胞生长因子的表达及与血管内皮功能的关系[J].中国老年学杂志,2017,37(9):2181-2182.
[15]马少雯,柳俊,梁润和,等.药物治疗对高血压及高血压并发冠心病患者肱动脉内皮依赖性舒张功能的影响[J].岭南心血管病杂志,2017,23(2):197-200,214.
[16]牛俊红,张静,周永安.间隙连接蛋白40基因多态性与原发性高血压病的相关性研究[J].中西医结合心脑血管病杂志,2014,12(5):548-550.
[17]LI X,DAI Y N,YAN S J,et al.Resveratrol lowers blood pressure in spontaneously hypertensive rats via calciumdependent endothelial NO production[J].Clin Exp Hypertens,2016,38(3):287-293.