王鹏丽^1，， 廖扬^2，， 雷敬辉^3，， 武烨^3，， 张苏丽^3，*， 刘慧荣^4，

（  1、首都医科大学生理学与病理生理学系；       2、首都医科大学基础医学院生理学与病理生理学系，；       3、首都医科大学基础医学院生理学与病理生理学系，北京，100069；       4、首都医科大学基础医学院生理学与病理生理学系；  ）

摘要： 目的：研究血管紧张素II 1型受体自身抗体（autoantibodies against angiotensin II type 1 receptor，AT1-AA）对人肾上腺皮质肿瘤细胞系(H295R细胞)分泌醛固酮（aldosterone，ALD）的影响及其机制。方法：利用杂交瘤技术制备AT1-AA，用不同浓度AT1-AA和血管紧张素（angiotensin II，Ang II）分别作用于H295R细胞6/12/24/48/72h，用放射免疫法检测细胞上清中ALD含量；用Western Blot检测合成ALD的限速酶CYP11B2的表达变化；观察血管紧张素II 1型受体(angiotensin II type 1 receptor，AT1R)特异性阻断剂缬沙坦和人工合成的AT1R胞外第二环肽段（the second extracellular loop of angiotensin II type 1 receptor，AT1-ECII）对AT1-AA的阻断效应。结果：10-6mol/L、10-7mol/L（高浓度）AT1-AA在72h时可促进ALD分泌，10-8mol/L、10-9mol/L（低浓度）AT1-AA在72h时可抑制ALD分泌；缬沙坦和AT1-ECII可以阻断醛固酮分泌减少的效应；同时10-9mol/L AT1-AA在72h时可抑制CYP11B2表达。结论：高浓度和低浓度AT1-AA对醛固酮分泌的作用相反，低浓度AT1-AA长时作用可通过H295R细胞上的AT1R抑制ALD分泌，这可能与AT1-AA抑制ALD合成酶CYP11B2的表达有关。
关键词： 醛固酮，血管紧张素II 1型受体，自身抗体，醛固酮合成酶，子痫前期

Wang Pengli^1,， Liao Yang^2,， Lei Jinghui^3,， Wu Ye^4,， Zhang Suli^4,*， Liu Huirong^4,

（  1、School of Basic Medical Sciences, Capital Medical University, Beijing, 100069；       2、School of Basic Medical Sciences, Capital Medical University,Beijing 100069；       3、School of Basic Medical Sciences, Capital Medical University, beijing, 100069；       4、School of Basic Medical Sciences, Capital Medical University, Beijing, 100069；  ）

Abstract： To explore the effect and mechanism of autoantibodies against angiotensin II type 1 receptor (AT1-AA) on aldosterone (ALD) secretion of human adrenocortical cell lines (H295R). Method: Hybridoma technology was used to prepare AT1-AA. Different concentration of AT1-AA and angiotensin II (Ang II) were added into H295R cells for 6/12/24/48/72h, ALD levels in the supernate were analyzed by radioimmunoassay, Western Blot was used to analyze the changes of the rate-limiting enzyme of ALD synthetase-CPY11B2, and the blocking effects of angiotensin II type 1 receptor (AT1R) specific blocker valsartan and synthetic second extracellular loop of angiotensin II type 1 receptor (AT1-ECII) antigen peptides were observed. Results: H295R cells treated with high concentration of AT1-AA in 10-6mol/L and 10-7mol/L for 72h can increase the ALD's secretion, whereas low concentration of AT1-AA in 10-8mol/L and 10-9mol/L can decrease the ALD's secretion by H295R cells after 72h incubation. After treatment with valsartan and AT1-ECII, the effect of AT1-AA-induced down-regulated ALD's secretion can be blocked. Additionally, AT1-AA in 10-9mol/L can inhibit the expression of CYP11B2. Conclusion: AT1-AA in high concentration and low concentration have different effect on ALD's secretion; low concentration of AT1-AA can inhibit the ALD's secretion by H295R cells via AT1R, and this effect may be due to the inhibition of expression of ALD synthetase-CYP11B2 caused by AT1-AA.
Keywords： aldosterone, angiotensin II type 1 receptor, autoantibody, CYP11B2, preeclampsia

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