丙泊酚对新生小鼠下丘脑室旁核神经元及下丘脑小胶质细胞的影响

发布时间：2018-12-14 04:59

【摘要】：目的研究丙泊酚对新生小鼠下丘脑区域神经元激活及小胶质细胞活化水平的影响,并探讨与丙泊酚神经毒性的相关性。方法 15只同窝7 d龄(postnatal day 7,P7)C57小鼠按随机数字表法分为3组(n=5):对照组、丙泊酚低剂量组、丙泊酚高剂量组。P7时,丙泊酚低、高剂量组小鼠分别接受丙泊酚30、60 mg/kg腹腔注射,对照组注射同等体积的脂肪乳溶剂。24 h后(P8)处死小鼠收取脑标本,采用免疫组织化学方法检测下丘脑C-Fos、精氨酸加压素(arginine vasopressin,AVP)、糖皮质激素受体(glucocorticoid receptor,GR)及小胶质细胞标志物离子钙接头分子蛋白1(ionized calcium binding adapter molecule 1,Iba1)的表达,Western blot测定AVP及GR的表达。结果与对照组(9.95±1.51)相比,丙泊酚低剂量组(14.75±1.39)、丙泊酚高剂量组(24.00±5.25)室旁核C-Fos阳性细胞数量均明显增多(P0.05,P0.01),且高剂量组相对低剂量组增多(P0.01);对照组(14.94±3.39)与低剂量组(19.63±3.70)室旁核表达AVP阳性细胞数量无明显差异,而高剂量组(23.38±2.29)中AVP阳性细胞数量对比对照组明显增加(P0.01),且蛋白表达上调;高剂量组(37.38±3.17)下丘脑室旁核GR表达相对对照组(27.38±2.17)及低剂量组(31.38±2.39)均明显上调(P0.01,P0.05),对照组和低剂量组间无差异;与对照组相比,低剂量组、高剂量组下丘脑背内侧区、腹内侧区、外侧区Iba1标记的小胶质细胞数量均明显减少。结论丙泊酚激活新生小鼠下丘脑室旁核神经元,致下丘脑精氨酸加压素和糖皮质激素受体表达上调,并抑制小胶质细胞活化水平,影响程度与剂量相关。
[Abstract]:Objective to study the effects of propofol on the activation of hypothalamic neurons and microglia in neonatal mice and to explore the relationship between propofol neurotoxicity and neurotoxicity. Methods Fifteen (postnatal day 7 P7) C57 mice were randomly divided into 3 groups: control group, propofol low dose group, propofol high dose group, P7, propofol low dose, propofol low, propofol high dose, propofol low, propofol low. The mice in the high dose group were injected with propofol for 60 mg/kg, and the control group was injected with the same volume of fat emulsion solvent. After 24 hours (P8), the mice were killed to collect brain samples, and the hypothalamic C-Foss were detected by immunohistochemical method. The expression of arginine vasopressin (arginine vasopressin,AVP), glucocorticoid receptor (glucocorticoid receptor,GR) and microglia marker ion-calcium junction molecular protein 1 (ionized calcium binding adapter molecule 1 (IBA 1) was detected by, Western blot. The expression of AVP and GR was measured. Results compared with the control group (9.95 卤1.51), the number of C-Fos positive cells in the paraventricular nucleus of the low dose propofol group (14.75 卤1.39) and the propofol high-dose group (24.00 卤5.25) was significantly increased (P0.05 卤P0.01). And the high dose group was higher than the low dose group (P0.01). There was no significant difference in the number of AVP positive cells between the control group (14.94 卤3.39) and the low dose group (19.63 卤3.70), while the number of AVP positive cells in the high dose group (23.38 卤2.29) was significantly higher than that in the control group (P0.01). The protein expression was up-regulated. The expression of GR in the paraventricular nucleus of the hypothalamus in the high dose group (37.38 卤3.17) was significantly higher than that in the control group (27.38 卤2.17) and the low dose group (31.38 卤2.39) (P 0.05). There was no difference between the control group and the low dose group. Compared with the control group, the number of Iba1 labeled microglia in the low dose group and the high dose group was significantly decreased in the dorsal medial area, ventromedial area and lateral area of the hypothalamus. Conclusion propofol activates the neurons in the paraventricular nucleus of hypothalamus of newborn mice, which leads to the up-regulation of arginine vasopressin and glucocorticoid receptor expression in hypothalamus, and inhibits the activation of microglia.
【作者单位】：第三军医大学新桥医院麻醉科;第三军医大学心理学院发育神经心理学教研室;
【分类号】：R722.1

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