低浓度血管紧张素II 1型受体自身抗体抑制人肾上腺皮质肿瘤细胞系醛固酮分泌
Low-concentration of Autoantibodies Against Angiotensin II Type 1 Receptor Inhibit the Aldosterone's Secretion of Human Adrenocortical Cell Lines
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。
o 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.
武烨、张苏丽、刘慧荣、王鹏丽、廖扬、雷敬辉
基础医学生理学生物化学
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
aldosterone angiotensin II type 1 receptor autoantibody CYP11B2 preeclampsia
武烨,张苏丽,刘慧荣,王鹏丽,廖扬,雷敬辉.低浓度血管紧张素II 1型受体自身抗体抑制人肾上腺皮质肿瘤细胞系醛固酮分泌[EB/OL].(2016-07-20)[2025-08-11].http://www.paper.edu.cn/releasepaper/content/201607-214.点此复制
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