黄芪百合颗粒通过HIF-1α-VEGF信号通路对常压缺氧模型小鼠脑损伤的保护作用

Protective effect of Huangqi Baihe Granule o0n brain injury in normobaric hypoxia mod⁃el mice through HIF-1α-VEGF signal pathway

目的观察黄芪百合颗粒通过HIF-1α-VEGF信号通路对常压缺氧环境下小鼠大脑损伤的保护作用。方法72只SPF级昆明种雄性小鼠随机分为空白组、模型组、阳性药组、黄芪百合颗粒低、中、高剂量组。空白组和模型组小鼠给予蒸馏水灌胃,黄芪百合颗粒低、中、高剂量组分别给与(1.75、3.5、7mg·kg^(-1))黄芪百合颗粒灌胃,阳性药组给与0.5mg(kg·d)枸杞红景天胶囊溶液灌胃,干预30d。灌胃的第5天开始,进行小鼠常压耐氧实验。分光光度法检测脑组织总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量、HE染色观察脑组织的病理形态学改变。Western blot检测各组小鼠HIF-1α、VEGF蛋白的表达水平。RT-PCR检测各组小鼠HIF-1α、VEGF mRNA的表达水平;结果与空白组相比,模型组小鼠病理切片可见细胞水肿明显出现多灶性神经元细胞坏死,周围有淋巴细胞等的炎性浸润,大脑指数明显升高,脑丙二醛(MDA)含量、HIF-1α、VEGF蛋白和mRNA含量明显升高(P<0.01),脑总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性明显降低(P<0.01);与模型组相比,黄芪百合颗粒高剂量组神经元细胞水肿、坏死明显减少,其大小、形态未发生明显变化,局部炎性浸润减少。黄芪百合颗粒低、中、高剂量组小鼠大脑指数、脑脑总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性明显升高(P<0.01或P<0.05),丙二醛(MDA)含量、VEGF蛋白和mRNA含量均明显降低(P<0.01或P<0.05)。结论黄芪百合颗粒可通过HIF-1α-VEGF信号通路对常压缺氧损伤的小鼠脑组织发挥良好的保护作用。

Objective To observe the protective effect of Huangqi Baihe Granule on brain injury in mice under normobaric hypox⁃ia through HIF-1α-VEGF signal pathway.Methods 72SPF Kunming male mice were randomly divided into blank group,model group,positive drug group,Huangqi Baihe granule low,medium and high dose groups.The mice in blank group and model group were given distilled water by gavage,the low,middle and high dose groups of Huangqi Baihe granule were given(1.75,3.5,7 mg·kg^(-1))Huangqi Baihe granule respectively,and the positive drug group was given 0.5mg·(kg·d^(-1))wolfberry Rhodiola capsule solution by gavage for 30 days.From the 5th day after gavage,the mice were subjected to normal pressure oxy⁃gen tolerance test.The total antioxidant capacity(T-AOC),superoxide dismutase(SOD),malondialdehyde(MDA)content in brain tissue were detected by spectrophotometry,and the pathological changes of brain tissue were observed by HE staining.The expression levels of HIF-1αand VEGF were detected by Western blot.HIF-1αand VEGF were detected by RT-PCR Re⁃sults:compared with the blank group,the pathological sections of the model group showed obvious cell edema,multifocal neuro⁃nal necrosis,inflammatory infiltration of lymphocytes and so on,the brain index was significantly increased,the content of brain malondialdehyde(MDA),HIF-1α,VEGF protein and mRNA content were significantly increased(P<0.01),the total an⁃tioxidant capacity(T-AOC)and superoxide were significantly increased in the model group Compared with the model group,the edema and necrosis of neurons in the high-dose Huangqi Baihe granule group were significantly reduced,and their size and mor⁃phology did not change significantly,and the local inflammatory infiltration was reduced.The brain index,MDA content,VEGF protein and mRNA content in the low,middle and high dose groups of Huangqi Baihe granule were significantly decreased(P<0.01 or P<0.05),The total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)activity were significantly in⁃creased(P<0.01or P<0.05).Results Conclusion Huangqi Baihe granule can protect the brain tissue of mice from hypoxia injury by HIF-1α-VEGF signal pathway.