G蛋白偶联的雌激素受体增加去卵巢小鼠补钙后的血管内皮炎性反应G protein-coupled estrogen receptor increases vascular endothelial inflammatory response after ovariectomized mice
范丽娜,魏巍,宁华,孙长颢
摘要(Abstract):
目的研究雌激素缺乏状态下补钙对血管内皮炎症反应的影响,及G蛋白偶联的雌激素受体可能发挥的作用及机制。方法将40只8周龄健康雌性C57BL/6小鼠按体重随机分为4组,分别为假手术对照组、去卵巢模型组、高钙组、植入G蛋白偶联的雌激素受体(G protein-coupled estrogen receptor, GPER)特异性激动剂G1+高钙组,每组10只。小鼠适应性喂养1周后行双侧去卵巢手术,假手术组仅切除卵巢周围部分脂肪组织。假手术组和去卵巢模型组喂饲AIN-93G基础饲料(钙含量0.5%),高钙组和植入G1+高钙组喂饲高钙饲料(调整的AIN-93G,钙含量1.5%)。3个月后,植入G1+高钙组小鼠皮下植入G1,每天0.2 mg/kg,其余组皮下植入安慰剂。28 d后,麻醉状态下心脏采血,检测血清血管内皮细胞粘附因子1(vascular endothelial adhesion factor-1,VCAM-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、雌二醇和血钙浓度;取主动脉弓做免疫组化检测瞬时受体电位通道1(transient receptor potential channel 1,TRPC1)、磷酸化细胞外信号调节激酶(phosphorylated-extracellular regulated kinase, p-ERK)1/2、VCAM-1以及CD68表达水平。结果去卵巢组小鼠体重高于假手术组(P<0.05),单独补钙或补钙联合植入G1组体重与去卵巢模型组相比差异无统计学意义(P>0.05)。摄食量各组间差异均无统计学意义(P>0.05)。去卵巢小鼠血清雌二醇水平低于假手术组(P<0.05)。补钙组血钙浓度高于未补钙组(P<0.05)。去卵巢小鼠血清VCAM-1浓度高于假手术组(P<0.05),单纯补钙组血清VCAM-1浓度高于去卵巢模型组(P<0.05),而补钙联合植入G1组血清VCAM-1浓度与去卵巢模型组相比差异无统计学意义(P>0.05)。TNF-α浓度各组间差异均无统计学意义(P>0.05)。单纯补钙组小鼠TRPC1、p-ERK1/2、VCAM-1和CD68表达高于去卵巢模型组(P<0.05),而补钙联合植入G1组上述指标均低于单纯补钙组(P<0.05),与去卵巢模型组相比差异无统计学意义(P>0.05)。结论雌激素缺乏状态下,补钙引发炎症反应增加,可能与GPER的活性改变,进而影响TRPC1/ERK1/2通路有关。
关键词(KeyWords): G蛋白偶联的雌激素受体;去卵巢;补钙;血管内皮细胞粘附因子-1
基金项目(Foundation):
作者(Author): 范丽娜,魏巍,宁华,孙长颢
DOI: 10.19813/j.cnki.weishengyanjiu.2021.02.019
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