摘要
目的探究丙泊酚对孕中期大鼠子代神经元自噬、记忆功能及c PKCγ的影响。方法取孕14 d的SD大鼠36只,随机分为对照组、丙泊酚组和丙泊酚+cPKCγ抑制剂组,每组12只。每组随机选择10只孕鼠,继续妊娠直至生下子鼠,出生30~34 d子鼠行Morris水迷宫实验;采用蛋白印迹试验检测海马组织中微管相关蛋白轻链3Ⅱ/Ⅰ(LC3Ⅱ/LC3Ⅰ)、贝林蛋白-1(Beclin-1)及cPKCγ、生长相关蛋白-43(GAP-43)蛋白表达;采用荧光检测海马组织中自噬相关蛋白ATG7表达。结果出生后31、32、33、34 d丙泊酚组和丙泊酚+cPKCγ抑制剂组子鼠逃避潜伏期长于对照组(P<0.05);和丙泊酚组相比,丙泊酚+cPKCγ抑制剂组子鼠逃避潜伏期明显缩短(P<0.05)。和对照组相比,丙泊酚组和丙泊酚+cPKCγ抑制剂组子鼠穿越平台次数明显减少(P<0.05);和丙泊酚组相比,丙泊酚+cPKCγ抑制剂组子鼠穿越平台次数明显增加(P<0.05)。和对照组相比,丙泊酚组和丙泊酚+c PKCγ抑制剂组子鼠在Ⅰ象限停留时间增加(P<0.05),在Ⅱ象限停留时间减少(P<0.05);和丙泊酚组相比,丙泊酚+cPKCγ抑制剂组子鼠在Ⅰ象限停留时间减少(P<0.05),在Ⅱ象限停留时间增加(P<0.05)。和对照组相比,丙泊酚组和丙泊酚+cPKCγ抑制剂组子鼠海马组织中LC3Ⅱ/LC3Ⅰ比值、Beclin-1、cPKCγ、GAP-43蛋白表达均明显增加(P<0.05);和丙泊酚组相比,丙泊酚+cPKCγ抑制剂组子鼠海马组织中LC3Ⅱ/LC3Ⅰ比值、Beclin-1、cPKCγ、GAP-43蛋白表达均明显减少(P<0.05)。和对照组相比,丙泊酚组和丙泊酚+cPKCγ抑制剂组子鼠海马组织中ATG7表达均明显增加(P<0.05);和丙泊酚组相比,丙泊酚+cPKCγ抑制剂组子鼠海马组织中ATG7表达均明显减少(P<0.05)。结论丙泊酚可导致孕中期大鼠子代认知功能障碍,促进神经元自噬,抑制海马组织中cPKCγ/GAP-43通路激活可能改善子代的认知功能障碍。
Objective Objective To explore the effects of Propofol on neuronal autophagy,memory function,and the classical protein kinase Cγ(cPKCγ)-related pathway in the offspring of rats during the second trimester of pregnancy.Methods Thirty-six SD rats at 14 d of gestation were randomly divided into the control group,the Propofol group and the Propofol+cPKCγinhibitor group,with 12 rats in each group.Ten pregnant mice were randomly selected from each group.The pregnancy continued until the offspring mice were born.The Morris water maze test was performed on the offspring mice at 30-34 d after birth.Western blotting was used to detect microtubule-associated protein light chain 3Ⅱ/Ⅰ(LC3Ⅱ/LC3Ⅰ),Beclin-1,cPKCγand growth-associated protein-43(GAP-43)expression levels in hippocampal tissue,and immunofluorescence was used to determine the expression of autophagy-related protein ATG7 in hippocampal tissue.Results Compared with the control group,the Propofol group and the propofol+cPKCγinhibitor group showed increased escape latency at 31,32,33 and 34 d after birth(P<0.05),while there was significantly decreased escape latency in the Propofol+cPKCγinhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγinhibitor group had significantly decreased number of platform crossings(P<0.05),while there was significantly increased number of platform crossings in the Propofol+cPKCγinhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγinhibitor group had increased time spent in quadrant I and decreased time spent in quadrantⅡ(P<0.05),while there was decreased time spent in quadrantⅠand increased time spent in quadrantⅡin the Propofol+cPKCγinhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the LC3Ⅱ/LC3Ⅰratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol group and the Propofol+cPKCγinhibitor group were significantly increased(P<0.05).Compared with the Propofol group,the LC3Ⅱ/LC3Ⅰratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol+cPKCγinhibitor group was significantly decreased(P<0.05).Compared with the control group,the expression of ATG7 in the hippocampal tissue of offspring rats in both the Propofol group and the Propofol+cPKCγinhibitor group was significantly increased(P<0.05).Compared with the propofol group,the expression of ATG7 in the hippocampal tissue of offspring rats in the Propofol+cPKCγinhibitor group was significantly decreased(P<0.05).Conclusion Propofol can cause cognitive impairment in the offspring of rats during the second trimester of pregnancy,promote neuronal autophagy,and inhibit activation of the cPKCγ/GAP-43 pathway in the hippocampus,which may improve cognitive impairment in the offspring rats.
作者
邓元荣
黄晓敏
陈立
DENG Yuanrong;HUANG Xiaomin;CHEN Li(Pharmacology Teaching and Research Office,Fujian Health Vocational and Technical College,Fuzhou,Fujian 350101,China;Department of Pharmacy,Fujian Provincial Hospital,Fuzhou,Fujian 350001,China)
出处
《免疫学杂志》
2025年第6期395-401,共7页
Immunological Journal
基金
福建省自然科学基金面上项目(2023J01170)。
