机构地区:[1]成都中医药大学药学院药理学教研室,成都610075 [2]四川大学华西基础医学与法医学院药理学研究室,成都610041
出 处:《四川大学学报(医学版)》2011年第4期503-507,共5页Journal of Sichuan University(Medical Sciences)
基 金:成都中医药大学科技发展基金(ZRYB200939)资助
摘 要:目的观察人参皂苷Rg1对新生鼠缺氧缺血性脑损伤(HIBD)后血管再生的影响,并探讨其可能机制。方法 10日龄SPF级SD大鼠54只,随机分为假手术组(n=6)、模型组(n=24)和Rg1组(n=24)。模型组及Rg1组采用单侧结扎颈总动脉并低氧通气制备新生鼠HIBD模型;假手术组仅分离右侧颈总动脉,不结扎,不进行低氧通气。Rg1组于术后即刻腹腔内注射0.1 mL含Rg1(40 mg/kg)的生理盐水,此后每隔24 h按相同剂量注射Rg1,共注射3 d;模型组和假手术组相同时间点腹腔内注射0.1 mL生理盐水。术后观察动物一般情况,于术后4、8、24、72 h处死大鼠取右侧脑组织,采用Western blot及免疫组织化学染色检测缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)蛋白表达;Ⅷ因子相关抗原(vwf)免疫组织化学染色标记微血管。结果术后新生大鼠均存活至实验完成。与假手术组比较,模型组和Rg1组均出现不同程度的神经行为学异常。模型组4、8、247、2 h各时间点HIF-1α蛋白表达均较假手术组增加(P<0.05),Rg1组各时间点HIF-1α蛋白表达水平均较同一时间点模型组上调(P<0.05)。模型组4、8、24 h VEGF蛋白表达较假手术组增加(P<0.05),Rg1组247、2 h VEGF蛋白表达较同一时间点模型组增加(P<0.05)。模型组24 h和72 h脑缺血区vwf阳性细胞较假手术组增多(P<0.05),Rg1组72 h脑缺血区vwf阳性细胞数目较同一时间点模型组增加(P<0.05)。结论 Rg1通过增强并稳定HIF-1α/VEGF信号轴,促进新生鼠HIBD后血管再生。Objective To investigate effects of ginsenoside Rg1 on angiogenesis in neonatal rats with hypoxia ischemia brain damage(HIBD), and explore the possible mechanism.Methods Fifty-four of 10-day-old SD rats were randomly divided into sham-operation group(n=6),hypoxia-ischemia brain damage group(n=24) and ginsenoside Rg1 treatment group(n=24).SD rats in HIBD group and Rg1 group were treated by separation and ligation of right common carotid artery(CCA) and subsequently exposed to hypoxia for 2.5 hours,and those in sham group were treated by only separation of right CCA,without ligation or exposure to hypoxia.Intraperitoneal injection of 0.1 mL normal saline(NS) containing 40 mg/kg Rg1 was performed immediately after operation in Rg1 group,and such process was repeated every 24 h for 3 days.Intraperitoneal injection of 0.1 mL pure NS was performed in both HIBD group and sham group,in the same way as that of in Rg1 group.General state of SD rats after operation was monitored,4,8,24 and 72 hours after HIBD,animals were executed and the right side of brain tissue was separated for further process.Protein expression of both hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor(VEGF) were detected by both Western blot and immunohistochemistry.Immunohistochemistry for von willebrand factor(vwf) was used to labeling micro vessels.Results All rats survived to the end of the study and neurological dysfunction was observed in both HIBD group and Rg1 group,but not in sham group.Expression of HIF-1α protein in HIBD group was increased at 4,8,24 and 72 h,compared to that in sham group(P0.05).Expression of HIF-1α protein in Rg1 group was increased compared to that in HIBD group at the same time points(P0.05).Expression of VEGF protein in HIBD group was increased at 4,8,and 24 h,compared to that in sham group(P0.05).Expression of VEGF protein in Rg1 group was increased at 24 and 72 h compared to that in HIBD group at the same time point(P0.05).Number of vwf-
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