二氢杨梅素对小鼠局灶性脑缺血/再灌注损伤的抗凋亡作用及机制研究

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摘要目的探讨二氢杨梅素（DMY）对小鼠局灶性脑缺血再灌注（I/R）损伤的抗细胞凋亡作用和相关机制，从而研究DMY抗脑缺血损伤的保护机制。方法将雄性昆明种小鼠随机分为假手术组、I/R模型组及DMY（500 mg/kg）组。小鼠大脑中动脉阻塞/再灌注（MCAO/R）局灶性脑I/R损伤模型利用改良线栓法来进行制备与完善。DMY组术前连续灌胃给药10 d，每天1次，并在缺血前1 h及再灌注后12 h各给药1次。缺血3 h再灌注24 h后，取脑采用原位缺口末端标记法（TUNEL）进行凋亡检测，免疫组织化学法和实时荧光定量PCR法（RT-qPCR）分别检测凋亡相关因子Bcl-2相关X蛋白（Bax）及B细胞淋巴瘤-2蛋白（Bcl-2）蛋白及mRNA表达。结果与假手术组比较，在I/R模型组中，小鼠缺血脑组织中凋亡阳性细胞数量明显增高，凋亡相关因子Bcl-2蛋白及基因表达下降（P＜0.01），而Bax的蛋白及基因表达增强（均P＜0.01）。与I/R模型组比较，DMY组小鼠缺血脑组织凋亡阳性细胞率显著下降，Bcl-2蛋白及基因表达增强，Bax蛋白和基因表达下降（均P＜0.01）。结论DMY可减轻小鼠局灶性脑I/R损伤所致的细胞凋亡，其抗凋亡机制可能与DMY上调Bcl-2表达、下调Bax表达有关。

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	甘露
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关键词 ：二氢杨梅素, 脑缺血/再灌注损伤, 大脑中动脉阻塞, 细胞凋亡

Abstract：Objective To study the anti-apoptosis effect of dihydromyricetin (DMY)on acute focal cerebral ischemia/reperfusion(I/R)injury in mice.Methods Male Kunming mice were randomly divided into sham group,I/R group and DMY group (500 mg/kg).Mice model of I/R injury was established by middle cerebral artery occlusion (MCAO)using modified thread method.Daily intragastric administration of DMY was carried out 10 days before the surgery,and 1 hour before ischemia and 12 hours after reperfusion.The brain tissues of the mice were harvested after ischemia for 3 hours and reperfusion for 24 hours.Myocyte apoptosis in the cerebral I/R brain was detected with in situ terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL staining).The protein and mRNA expression of Bax and Bcl-2 were detected by immunohistochemistry assay and real-time quantitative PCR (RT-qPCR)respectively.Results Compared with sham group,apaotosis index was significantly higher,protein and mRNA expressions of Bcl-2 were lower than those of Bax were higher in I/R model group(all P＜0.01).Compared with I/R model group,in DMY group,apoptosis index decreased significantly,the expressions of Bcl-2 were higher,those of Bax were lower(all P＜0.01).Conclusion DMY can reduce the myocyte apoptosis induced by focal I/R injury,its anti-apoptotic mechanism might be related to regulating the expressionof Bax and Bcl-2.

Key words： Dihydromyricetin Cerebral ischemia/reperfusion injury Middle cerebral artery occlusion Apoptosis

基金资助:国家自然科学基金项目（81360056）；
广西壮族自治区南宁市科学研究与技术开发计划项目（20153105）

通讯作者: 郭哲（1975-），男，主治医师，研究方向：心脑血管急诊；何萍（1975-），女，博士，教授，研究方向：心脑血管药理学

作者简介: 甘露（1992-），男，硕士，研究方向：心脑血管药理学；邓之婧（1991-），女，硕士，研究方向：心脑血管药理学

引用本文:

甘露；邓之婧；王献哲；苏棋；梁聪；郭哲；何萍. 二氢杨梅素对小鼠局灶性脑缺血/再灌注损伤的抗凋亡作用及机制研究[J]. 中国当代医药, 2018, 25(14): 4-8.
GAN Lu；DENG Zhi-jing；WANG Xian-zhe；SHU Qi；LIANG Cong；GUO Zhe； HE Ping. Study on anti-apoptosis effect and mechanism of dihydromyrcetin on focal cerebral ischemia-reperfusion injury in mice. 中国当代医药, 2018, 25(14): 4-8.

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