丙泊酚對(duì)新生小鼠下丘腦室旁核神經(jīng)元及下丘腦小膠質(zhì)細(xì)胞的影響
發(fā)布時(shí)間:2018-12-14 04:59
【摘要】:目的研究丙泊酚對(duì)新生小鼠下丘腦區(qū)域神經(jīng)元激活及小膠質(zhì)細(xì)胞活化水平的影響,并探討與丙泊酚神經(jīng)毒性的相關(guān)性。方法 15只同窩7 d齡(postnatal day 7,P7)C57小鼠按隨機(jī)數(shù)字表法分為3組(n=5):對(duì)照組、丙泊酚低劑量組、丙泊酚高劑量組。P7時(shí),丙泊酚低、高劑量組小鼠分別接受丙泊酚30、60 mg/kg腹腔注射,對(duì)照組注射同等體積的脂肪乳溶劑。24 h后(P8)處死小鼠收取腦標(biāo)本,采用免疫組織化學(xué)方法檢測(cè)下丘腦C-Fos、精氨酸加壓素(arginine vasopressin,AVP)、糖皮質(zhì)激素受體(glucocorticoid receptor,GR)及小膠質(zhì)細(xì)胞標(biāo)志物離子鈣接頭分子蛋白1(ionized calcium binding adapter molecule 1,Iba1)的表達(dá),Western blot測(cè)定AVP及GR的表達(dá)。結(jié)果與對(duì)照組(9.95±1.51)相比,丙泊酚低劑量組(14.75±1.39)、丙泊酚高劑量組(24.00±5.25)室旁核C-Fos陽(yáng)性細(xì)胞數(shù)量均明顯增多(P0.05,P0.01),且高劑量組相對(duì)低劑量組增多(P0.01);對(duì)照組(14.94±3.39)與低劑量組(19.63±3.70)室旁核表達(dá)AVP陽(yáng)性細(xì)胞數(shù)量無(wú)明顯差異,而高劑量組(23.38±2.29)中AVP陽(yáng)性細(xì)胞數(shù)量對(duì)比對(duì)照組明顯增加(P0.01),且蛋白表達(dá)上調(diào);高劑量組(37.38±3.17)下丘腦室旁核GR表達(dá)相對(duì)對(duì)照組(27.38±2.17)及低劑量組(31.38±2.39)均明顯上調(diào)(P0.01,P0.05),對(duì)照組和低劑量組間無(wú)差異;與對(duì)照組相比,低劑量組、高劑量組下丘腦背內(nèi)側(cè)區(qū)、腹內(nèi)側(cè)區(qū)、外側(cè)區(qū)Iba1標(biāo)記的小膠質(zhì)細(xì)胞數(shù)量均明顯減少。結(jié)論丙泊酚激活新生小鼠下丘腦室旁核神經(jīng)元,致下丘腦精氨酸加壓素和糖皮質(zhì)激素受體表達(dá)上調(diào),并抑制小膠質(zhì)細(xì)胞活化水平,影響程度與劑量相關(guān)。
[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 鹵1.51), the number of C-Fos positive cells in the paraventricular nucleus of the low dose propofol group (14.75 鹵1.39) and the propofol high-dose group (24.00 鹵5.25) was significantly increased (P0.05 鹵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 鹵3.39) and the low dose group (19.63 鹵3.70), while the number of AVP positive cells in the high dose group (23.38 鹵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 鹵3.17) was significantly higher than that in the control group (27.38 鹵2.17) and the low dose group (31.38 鹵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.
【作者單位】: 第三軍醫(yī)大學(xué)新橋醫(yī)院麻醉科;第三軍醫(yī)大學(xué)心理學(xué)院發(fā)育神經(jīng)心理學(xué)教研室;
【分類號(hào)】:R722.1
本文編號(hào):2377969
[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 鹵1.51), the number of C-Fos positive cells in the paraventricular nucleus of the low dose propofol group (14.75 鹵1.39) and the propofol high-dose group (24.00 鹵5.25) was significantly increased (P0.05 鹵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 鹵3.39) and the low dose group (19.63 鹵3.70), while the number of AVP positive cells in the high dose group (23.38 鹵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 鹵3.17) was significantly higher than that in the control group (27.38 鹵2.17) and the low dose group (31.38 鹵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.
【作者單位】: 第三軍醫(yī)大學(xué)新橋醫(yī)院麻醉科;第三軍醫(yī)大學(xué)心理學(xué)院發(fā)育神經(jīng)心理學(xué)教研室;
【分類號(hào)】:R722.1
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