加味补阳还五汤对新生大鼠缺氧缺血性脑损伤低氧诱导因子-1表达的调控  

Buyang Huanwu Decoction Up-regulates the Expression of HIF-1 in Neonatal Rats Following Hypoxic-ischemic Brain Damage

作　　者：赵红梅[1] 王远照[1] 辛顺心 赵清宴[3] 

机构地区：[1]浙江中医药大学附属第一医院,杭州310018 [2]浙江省立同德医院 [3]浙江中医药大学

出　　处：《浙江中医药大学学报》2014年第12期1374-1377,共4页Journal of Zhejiang Chinese Medical University

摘　　要：[目的]建立新生SD大鼠缺氧缺血性脑损伤(HIBD)模型,观察低氧诱导因子-1(HIF-1)的表达及加味补阳还五汤对新生大鼠缺氧缺血性脑损伤的保护作用,为新生儿缺氧缺血性脑损伤提供新的治疗思路。[方法]新生7d龄SD大鼠140只,随机分为空白组(28只)、HIBD模型组(28只)及加味补阳还五汤组(84只),加味补阳还五汤组按给药剂量分为高、中、低剂量组。每组分别在规定时间点处死,光镜下观察各组大鼠左侧脑组织HE染色的病理改变、组织中HIF-1α蛋白表达,并通过RT-PCR检测HIF-1基因表达。[结果]缺氧缺血后新生大鼠出现不同程度的行为异常,1h后逐渐由兴奋转为抑制,少数发生抽搐;HE染色结果显示,加味补阳还五汤高剂量组各时间点损伤程度比中、低剂量组均有明显减轻;免疫组化结果显示,加味补阳还五汤各剂量组各时间点HIF-1α阳性细胞数均较空白组多,高剂量组各时间点HIF-1α阳性细胞数均较HIBD组明显增多;荧光定量PCR检测结果表明加味补阳还五汤高剂量组HIF-1的表达量高于其他组,差异均有统计学意义(P<0.05)。[结论]加味补阳还五汤能通过上调HIF-1的表达来减轻缺氧缺血所致的脑损伤,此研究为临床治疗新生儿缺氧缺血性脑损伤提供了新的治疗思路。[Objective] This experiment set up hypoxic-ischemic brain damage（HIBD） model, to observe the HIF-1 αexpression of brain tissue in neonatal rats following HIBD, and explore the possible neuroprotective mechanisms of Buyang Huanwu Decoction. The experiment result could provide theoretical basis to the clinical application of Buyang Huanwu Decoction.[Methods] A total of 140 seven-day-old SD rats were randomly divided into three groups：blank group, hypoxic-ischemic brain damage（HIBD） group and Buyang Huanwu Decoction group（BYHW group）. According to different dosage,BYHW group was divided into the high-dose group, middle-dose group and low-dose group. Rats were sacrificed at different time points, to observe morphological changes in brain tissue in general. After HE coloration, pathological changes of left brain tissue of all subjects were observed under light microscope. The HIF-1α expression in brain tissue was detected by IHC and the m RNA level of HIF-1 was determined by FQ-PCR technique.[Results] Neonatal rats had various abnormal behaviors after HIBD： the rats were depressed after one hour later, and a few of them had convulsion. HE staining： rats in high-dose group of Buyang Huanwu Decoction, had more significantly pathological changes in brain tissue in every time points than that in the HIBD model group, middle-dose group or low-dose group. Immunohistochemical results showed more HIF-1 αpositive cells existed in the brain tissue of BYHW group, compared with that of blank group and HIBD group, especially in BYHW high dose group（ P〈0.05）.FQ-PCR result indicated that HIF-1α protein expression was significantly higher in high-dose group of Buyang Huanwu Decoction than in any other group（ P 0.05）.[Conclusion] These results suggested that Buyang Huanwu Decoction has pathologically neuroprotective effect to neonatal rats following HIBD and can relieve the pathologic damage. Buyang Huanwu Decoction could upregulate the expression of HIF-1 α, alleviate pathological impact of HIBD. This

关 键 词：缺氧缺血性脑损伤 新生大鼠 加味补阳还五汤 剂量 低氧诱导因子-1 实验研究 

分 类 号：R331[医药卫生—人体生理学]