摘要
目的从蛋白质和基因水平探讨血管紧张素Ⅱ１Ａ（ＡＴ１Ａ）受体在大鼠肾小管间质病变过程中的作用机理及转换酶抑制剂的调节作用。方法大鼠单侧输尿管结扎术后，分为两组，治疗组用转换酶抑制剂（苯那普利）５０ｍｇ／Ｌ置自来水中喂饲，在手术前２４小时开始喂饲直至将大鼠处死时止。对照组单纯用自来水喂饲。利用免疫组化及原位杂交方法观察ＡＴ１Ａ受体表达，并同时测定血压和观察组织学变化。结果单侧输尿管梗阻术后１０天，对照组大鼠平均动脉压升高（１６．６±０．７ｋＰａ）并出现明显的肾小管间质改变，治疗组肾小管间质病变明显减轻，平均动脉压降低（１４．２±０．６ｋＰａ），两组比较Ｐ＜０．０５，免疫组化和原位杂交结果显示对照组肾小管上皮细胞、肾间质及血管周围有大量ＡＴ１Ａ受体表达，而治疗组ＡＴ１Ａ受体表达明显减弱。结论肾小管间质损伤时可以使ＡＴ１Ａ受体表达上调。苯那普利可以减少ＡＴ１Ａ受体表达，减缓肾小管间质的损伤，从而进一步解释了肾脏局部的血管紧张素Ⅱ可能主要是与ＡＴ１Ａ受体的结合而产生作用。
Objective To study the expressions of angiotensin Ⅱ1A receptor (AT1A) both at the mRNA level and the protein level and their modulation by an angiotensin converting enzyme inhibitor, benazepril, in the renal tubulointerstitial injuries induced by unilateral ureteral obstruction (UUO) in rats. Methods Six SD rats (UUO T) were administered benazepril in the drinking water (50mg/L). Additional 6 rats were used as untreated controls (UUO C). Mean arterial Prossure (MAP) was measured at the 10th day after UUO, and then all animals were sacrificed. The expressions of AT1A were examined both at the mRNA level by in situ hybridization using a subtype specific probe and at the protein level by an immunohistochemistry methods using AT1 receptor antibody in normal rat kidneys and the obstructed rat kidneys. Results MAP was 14.2±0.6kPa in the UUO T and 16.6±0.7 kPa in the UUO C ( P < 0.05). Benazepril slowed the tubulointersititial fibrosis (TIF) and reduced the expression of AT1A in the renal tubular epithelial cells, the interstitial areas, and the walls of renal arteriole in the UUO T group. Conclusion The increased expressions of AT1A were found in the acute renal tubulointerstitial pathogenesis induced by UUO. Benazepril may retard the progression of TIF and decrease the expression of AT1A in the obstructed kidneys. We conclude that the effects of Ang Ⅱ on the obstructed kidneys may be due to its binding with AT1A.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1997年第4期245-248,T003,共5页
National Medical Journal of China
基金
国家自然科学基金
优秀中青年人才专项基金
关键词
输尿管梗阻
受体
血管紧张素
基因表达
Unilateral ureteral obstruction Receptors angiotensin Gene expression
