雌二醇、G蛋白耦联雌激素受体激动剂和抑制剂对去势大鼠5-羟色胺水平的影响

Effects of estrogen,G-protein coupled estrogen receptor agonists and inhibitors on 5-hydroxytryptamine levels in ovariectomized rats

目的探索雌激素对去势大鼠血清5-羟色胺(HT)水平的影响,以及G蛋白耦联雌激素受体(GPER)在其中发挥的作用。方法健康12周龄性成熟雌性大鼠50只,随机分为10组,每组5只。其中30只通过卵巢去势手术建立绝经大鼠模型,20只行假手术作为对照组。去势大鼠再分为6组,分别注射1周的雌二醇(E_2)组、E_2+GPER特异性激动剂(G1)组、G1组、抑制剂(G15)组、E_2+G15组、油剂组;假手术大鼠分别注射1周的G1组、G15组、空白组、油剂。于手术前及用药前后分别进行心脏采血,采用酶联免疫吸附法(ELISA)检测血清中5-HT的水平。结果大鼠卵巢去势手术后5-HT水平显著降低(P=0.031),假手术后5-HT水平无显著变化(P=0.380)。卵巢去势的大鼠在连续注射1周E_2后,5-HT水平显著升高(P=0.007)。单独注射G1或G15及E_2+G1或E_2+G15 1周后,5-HT水平变化均无统计学意义。结论大鼠卵巢去势后血清5-HT水平显著降低,而使用雌激素治疗使5-HT水平升高,G1和G15治疗1周对大鼠5-HT水平没有显著影响。

Objective To explore the effect of estrogen on 5-hydroxytryptamine （5-HT） levels in ovariectomized rats and the role of the G protein-coupled estrogen receptor （GPER） in it. Methods Fifty 12-week-old female mice were randomly divided into two groups in which 30 rats were ovariectomized to establish the model of menopause, the other 20 rats were sham-operated. Ovariectomized rats were subdivided into 6 groups, including injection with estradiol （E2）, Ez＋GPER specific agonist （G1）, G1, inhibitor （G15）, E2＋G15, oil for one week; sham operation rats were injected with G1, G15, blank and oil for 1 week. Blood samples were taken from the heart before operation, and before and after treatment. Serum 5-HT levels were measured by enzyme-linked immunosorbent assay （ELISA）. Results After ovariectomy, the level of 5-HT was significantly decreased （P=0.031） in rats and the level of 5-HT did not change significantly after sham operation （P=0.380）. Serum levels of 5-HT were significantly elevated in ovariectomized rats after one week of continuous injection of E2 （P=0.007）. There was no significant change in 5-HT levels after G1 or G15 injection alone or E2＋G1 or E2＋G15 injection after one week. Conclusion Serum 5-HT levels were significantly decreased after ovarian castration, whereas estrogen treatment resulted in elevated 5-HT levels. No significant effect of G1 and G15 on serotonin levels in rats was found. However, the mechanisms by which estrogen regulates mood disorders and 5-HT, and the role that GPER plays in them still need to be fin-ther explored and studied.