MRL lpr/lpr自发狼疮鼠血管紧张素Ⅱ受体的基因表达及其在发病中的作用

EXPRESSIONS OF ANGIOTENSINⅡ AT1A, AT1B AND AT2 RECEPTOR GENES AND ITS ROLE IN THE PATHOGENESIS OF MRL lpr/lpr MICE

目的：探讨血管紧张素Ⅱ受体在系统性红斑狼疮发病中的作用。方法：利用逆转录聚合酶链反应（ＲＴＰＣＲ）的方法检测ＭＲＬｌｐｒ／ｌｐｒ自发狼疮鼠和ＭＲＬ系小鼠８和１８周时肾、心、肺、肝、脑、垂体、肾上腺、睾丸、卵巢和子宫组织中血管紧张素ⅡＡＴ１Ａ、ＡＴ１Ｂ和ＡＴ２受体的基因表达。结果：在１８周龄ＭＲＬｌｐｒ／ｌｐｒ小鼠肾、心、肺、肝、脑和睾丸等明显受损伤的组织中，ＡＴ１Ａ受体的ｍＲＮＡ表达有显著升高，而ＡＴ１Ｂ和ＡＴ２受体的基因表达与ＭＲＬ小鼠８和１８周时及ＭＲＬｌｐｒｌ／ｌｐｒ小鼠末发病（８周龄）时比较则无明显改变。应用血管紧张素转化酶抑制剂盐酸苯那普利治疗后，１８周龄ＭＲＬｌｐｒ／ｌｐｒ小鼠的尿蛋白和肾、心、肺、肝、脑和睾丸组织中ＡＴ１Ａ受体的ｍＲＮＡ水平显著降低，但上述脏器的病理损伤无明显减轻。结论：ＡＴ１Ａ受体参与了狼疮导致的多脏器损伤过程并起到一定作用。

Aim: To investigate the role of angiotensin Ⅱ receptor in the pathogenesis of systemic lupus erythematous. Methods:Expressions of angiotensin Ⅱ AT1A, AT1B and AT2 receptor genes were examind by RT PCR in the kidney, heart, lung, liver, brain, pituitary, adrenal glands, testis, ovary and uterus of MRL and MRL/lpr/lpr mice at the age of 8 and 18 weeks, respectively. Results: The mRNA level of AT1A receptor gene was significantly increased in the lupus injured organs of kidney, heart, lung, liver, brain and testis of 18 week old MRL lpr/lpr mice as compared with in 8 and 18 week old MRL mice or 8 week old MRL lpr/lpr mice, but the expressions of AT1B and AT2 receptor genes were unchanged in those groups of mice. The levels of proteninuria and the mRNA expression of AT1A receptor in the injuried organs were markedly reduced by angiotensin converting enzyme inhibitor (benazepril) treatment, but the pathological damages were not alleviated markedly. Conclusion: The activated AT1A receptor partly contributed to the pathogenesis of lupus in the multiple organs of MRL lpr/lpr mice.