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[1]李蒙,何地芹,曹自为,等.丹参多酚酸介导PIDD通路改善大鼠缺血性脑损伤的机制研究[J].医学研究与战创伤救治(原医学研究生学报),2022,24(3):225-229.[doi:10.3969/j.issn.1672-271X.2022.03.001]
　LI Meng,HE Di-qin,CAO Zi-wei,et al.Salvianolicacids ameliorate cerebral ischemic injury via PIDD pathway in rats[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2022,24(3):225-229.[doi:10.3969/j.issn.1672-271X.2022.03.001]
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丹参多酚酸介导PIDD通路改善大鼠缺血性脑损伤的机制研究()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第24卷
期数:
2022年3期
页码:
225-229
栏目:
基础研究
出版日期:
2022-06-30

文章信息/Info

Title:
Salvianolicacids ameliorate cerebral ischemic injury via PIDD pathway in rats
作者:
李蒙; 何地芹; 曹自为; 管叶明; 黄海丽; 汪青松
作者单位：210048南京，南京江北医院神经内科（李蒙）；230031合肥，解放军联勤保障部队第九○一医院神经内科（何地芹、曹自为、管叶明、黄海丽、汪青松）
Author(s):
LI Meng;  HE Di-qin;  CAO Zi-wei; GUAN Ye-ming; HUANG Hai-li;  WANG Qing-song
（1.Department of Neurology，Nanjing Jiangbei Hospital，Nanjing 210048, Jiangsu, China；2.Department of Neurology, the 901th Hospital of the Joint Logistics Support Force，PLA，Hefei 230031, Anhui, China）
关键词:
丹参多酚酸; 缺血性脑损伤; p53诱导的死亡结构域蛋白
Keywords:
salvianolic acids; cerebral ischemic injury; p53-induced protein with a death domain(PIDD)
分类号:
R743.3
DOI:
10.3969/j.issn.1672-271X.2022.03.001
文献标志码:
A
摘要:
目的探讨注射用丹参多酚酸(SA)对大鼠脑缺血再灌注损伤的保护作用及其与p53诱导的死亡结构域蛋白(PIDD)通路的关系。方法选择40只健康雄性SD大鼠，随机均分为 4 组: 假手术组、缺血模型组、丹参多酚酸组、抑制剂组，每组10只。采用改良线栓法构建大鼠右侧大脑中动脉栓塞模型，改良的神经功能缺损评分(mNSS) 法评估神经功能缺损程度，逆转录-聚合酶链反应(RT-PCR) 法和Western blot法检测各组大鼠缺血再灌注后不同时间点（1 d、3 d、7 d）脑组织匀浆中PIDD mRNA及蛋白表达变化，以及7 d 半胱氨酸天冬氨酸酶2（caspase-2）、t-BID、细胞色素C、半胱氨酸天冬氨酸酶3（caspase-3）蛋白表达。取缺血再灌注后7 d脑组织，采用TUNEL法检测神经细胞凋亡情况，计算梗死灶脑组织神经细胞凋亡指数 (AI)。结果与缺血模型组比较，丹参多酚酸组在缺血再灌注后3 d、7 d 时神经功能缺损评分明显降低(P＜0. 01)；与抑制剂组比较，丹参多酚酸组缺血再灌注后3 d、7 d 神经功能缺损评分高于抑制剂组(P＜0. 01) 。丹参多酚酸组PIDD mRNA和蛋白的表达显著低于缺血模型组，高于抑制剂组（P<0.01）；丹参多酚酸组caspase-2、t-BID、细胞色素-c和caspase-3蛋白的表达显著低于缺血模型组，高于抑制剂组（P<0.01）。缺血模型组AI[（53.25±4.16）%]显著增加，丹参多酚酸组AI[（35.13±4.23）%]和抑制剂组AI[（24.5±5.14）%]均低于缺血模型组（P<0.05）。结论丹参多酚酸通过下调PIDD及其下游 半胱氨酸天冬氨酸酶2、t-BID、细胞色素-C和半胱氨酸天冬氨酸酶3的表达改善大鼠脑缺血损伤。
Abstract:
ObjectiveTo investigate the effect of salvianolic acids (SA) on cerebral ischemic injury via PIDD (p53-induced protein with a death domain) pathway.MethodsA total of 40 healthy male SD rats were randomly divided into 4 groups: sham operation group (Sham), ischemia model group (IS), SA group and PIDD inhibitor group (BubR1). Focal cerebral ischemia was induced in rats by occlusion of MCA for 2h. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of PIDD mRNA. PIDD, caspase-2, t-BID, cytochrome-c, and caspase-3 protein expression were detected by Western blot. The neurological deficits were assessed by modified Neurological Severity Scores (mNSS) at 1, 3, and 7 days after reperfusion. TUNEL-positive cells were considered to be undergoing apoptosis. The percentage of apoptosis (apoptotic index: AI) was determined as a percentage of the total cell number.ResultsCompared with IS group, the mNSS score in the SA group was significantly lower (P<0.01), while the mNSS score in SA group was higher than those in the BubR1 group (P<0.01) at 3 d and 7 d after reperfusion. The expression of PIDD mRNA and protein in SA group was significantly lower than that in IS group, but higher than that in BubR1 group (P<0.01). The expression of caspase-2, t-BID, cytochrome-c and caspase-3 protein was significantly lower than that in IS group and was higher than that in BubR1 group (P<0.01). The AI in the IS group was significantly increased [（53.25±4.16）%]. The AIs in SA group [（35.13±4.23）%] and BubR1 group [（24.5±5.14）%] were lower than that in IS group (P<0.05).ConclusionSA ameliorates cerebral ischemic injury in rat by down-regulation of PIDD and its downstream expression of caspase-2, t-BID, cytochrome-c and caspase-3.

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备注/Memo

备注/Memo:
基金项目：国家自然科学基金（81171108）；全军医药卫生科研基金（15MS047）
更新日期/Last Update: 2022-06-21