【作者】 胡洪贞；

【导师】 李伟；

【作者基本信息】 山东中医药大学 ， 中西医结合临床， 2010， 硕士

【摘要】 目的：利用自发性高血压大鼠(spontaneously hypertensive rat, SHR)模型,观察血管内皮功能障碍标志物与早期肾损害的相关性;同时,在SHR肾损害早期(16周龄始)给予加味天麻钩藤饮进行干预,观察其对SHR血管内皮功能及早期肾损害的作用,探讨效应途径和机制。方法：购买40只15周龄的同源同系、雄性SHR,适应性喂养一周,称重、标记终身号并随机分组,即模型对照组、加味天麻钩藤饮组、福辛普利组和联合于预组。观察模型对照组SHR 24小时尿蛋白定量与血清一氧化氮(nitric oxide, NO)、血浆(endothelin-1, ET-1)及循环NO/ET-1的相关性；同时,实验各组在高血压肾损害早期(16周龄始)给予相应干预药物,以观察加味天麻钩藤饮、福辛普利及两药联合应用后,对SHR血压、24小时尿蛋白定量、内生肌酐清除率(endogenous creatinine clearance rate, Ccr)、血清NO、血浆ET-1及循环NO/ET-1的影响。结果：1.模型组SHR24小时尿蛋白排泄量与血清NO呈负相关,Pearson系数为—0.818,P-0.047,P<0.05；与循环NO/ET-1呈负相关,Pearson系数为—0.835,P=0.039,P<0.05；与血清ET-1关系不明显,Pearson系数为0.058,P=0.913,P>0.05。2.加味天麻钩藤饮可以显著降低SHR脉压(pulse pressure, PP),与模型对照组相比,P<0.01；与福辛普利联合应用后,两者降压起协同作用。3.加味天麻钩藤饮可以显著降低血浆ET-1水平,与模型对照组相比,P<0.01；对血清NO水平影响不明显,P>0.05。4.加味天麻钩藤饮与福辛普利联合应用后,24小时尿蛋白定量明显下降,与模型对照组比较,P<0.01；循环NO/ET-1升高,与模型对照组比较,P<0.05。结论：1.SHR早期肾损害24小时尿蛋白排泄量与血清NO浓度及循环NO/ET-1水平呈负相关,推测高血压早期肾损害与血管内皮功能障碍(endothelial dysfunction, ED)有一定的相关性,尤与血管内皮舒张功能障碍密切相关。2.加味天麻钩藤饮单独应用,即可显著降低脉压,疗效与血管紧张素转化酶抑制剂(angiotensin-converting enzyme inhibitor, ACEI)福辛普利相当。3.加味天麻钩藤饮可以显著降低血浆ET-1水平,改善内皮依赖性收缩功能,推测具有一定的血管内皮保护作用。4.加味天麻钩藤饮与ACEI联合应用后,协同降压、进一步减轻早期肾损害,推测其机制可能与加味天麻钩藤饮的血管内皮保护作用有关。5.加味天麻钩藤饮与ACEI联合应用后,血管内皮功能及肾损害均有一定程度的改善,结合本实验结论1,推测改善血管内皮功能可能是干预高血压早期肾损害的新的有效途径。6.对高血压早期肾损害的防治,强调早期检测敏感指标,并结合辨证,给予加味天麻钩藤饮联合降压药物,进行多靶点干预,能够起到协同增效的作用,更好的保护靶器官功能。更多还原

【Abstract】 Objective:To observe the relationship between the vascular endothelial dysfunction and early kidney damage by using the model of spontaneously hypertensive rat (SHR); meanwhile, the SHR were fed with the decoction of Jiaweitianmagoutengyin in the early renal damage(16 weeks), to observe its effects on vascular endothelial function and early kidney damage, explore the channels and mechanisms simultaneously.Methods:40 homogenous 15-week-old male SHR were purchased, adaptive feeding for one week, then weigh, tag the life number and randomly divided into 4 groups, namely, model control group, Jiaweitianmagoutengyin group, Fosinopril group and the joint intervention group. The correlation between 24-hour urine protein excretion and serum NO, plasma ET-1 and circulating NO/ET-1 were observed through the model control group; Meanwhile, the experimental groups, were given corresponding drug-interventions in the early stage of hypertensive renal injury (16 weeks), the changes of blood pressure, 24-hour urine protein quantitative, creatinine clearance rate, serum NO, plasma ET-1 and circulating NO/ET-1 of SHR were observed after using Jiaweitianmagoutengyin decoction, Fosinopril and the combining use of both drugs.Results:1.In model control group,24-hour urine protein excretion was negatively correlated with plasma ET-1, Pearson coefficient was -0.818, P=0.047, P<0.01; and had a negative correlation with circulating NO/ET-1, too, Pearson coefficient was -0.835, P= 0.039, P<0.05; significant relationship between 24-hour urine protein excretion and serum NO was not found.2.Jiaweitianmagoutengyin decoction can significantly reduce the pulse pressure of SHR, P<0.01, play a synergistic effect of depressurization after combining use of Fosinopril.3.Jiaweitianmagoutengyin decoction can significantly reduce the plasma ET-1 level, P<0.01; no significant effect on serum NO level, P> 0.05.4. After combining use of Jiaweitianmagoutengyin decoction and Fosinopril, the 24-hour urinary protein quantitative decreased significantly, compared with the model control group, P <0.01; circulating NO/ET-1 increased compared with model control group, P<0.05.Conclusion:1.SHR’s 24 hours urinary protein excretion and serum nitric oxide concentration was negatively correlated, there was also a negative correlation between 24 hours urinary protein excretion and the level of circulating NO/ET-1, speculating that there was a certain degree of relevance between the early stage of hypertensive renal damage and vascular endothelial dysfunction.,especially the diastolic dysfunction.2.Independent use of Jiaweitianmagoutengyin decoction can significantly reduce the pulse pressure, has the equal efficacy compared with Fosinopril(ACEI).3. Jiaweitianmagoutengyin decoction has a good protective effect on vascular endothelium, particularly in reducing plasma ET-1 level, mainly to ameliorate the endothelium-dependent contraction.4.Combining use of Jiaweitianmagoutengyin decoction and Fosinopril(ACEI) showed a synergistic effect of depressurization, further ease early kidney damage, speculating its mechanism may be related to the role of vascular endothelial protection of Jiaweitianmagoutengyin decoction. 5.After combining use of Jiaweitianmagoutengyin decoction and Fosinopril(ACEI), vascular endothelial function and renal damage have improved to some extent,considering the first result of this experiment, speculating that improving vascular endothelial function is a new and effective way to intervene early hypertensive renal damage.6.For prevention and treatment of early hypertensive renal damage, we emphasize the early detection of sensitive indicators;combined with syndrome differentiation, joint use of Chinese medicine compound and antihypertensive drugs, multi-target interference,can play a synergistic role for protection of target organs.更多还原