摘要
目的:观察砭贴预处理对急性低压低氧脑损伤模型大鼠血清脯氨酸羟化酶2(PHD2)、低氧诱导因子1α(HIF-1α)含量的影响,探究砭贴预防高原脑损伤的可能作用机制。方法:将45只雄性SD大鼠随机分为空白组、模型组、砭贴组、药物组、砭贴抑制剂组,每组9只。砭贴组和砭贴抑制剂组大鼠予砭贴预处理,穴取“太渊”“内关”和“人迎”,每次2 h,每日1次;药物组大鼠每日按280 mg/kg剂量灌胃大株红景天胶囊药液,均干预14 d。砭贴抑制剂组于造模前24 h按40 mg/kg剂量腹腔注射PHD抑制剂二甲基乙二酰氨基乙酸(DMOG)。干预结束后,除空白组外,其余4组大鼠均采用氧舱模拟高原环境建立急性低压低氧脑损伤模型。检测各组大鼠动脉血血气分析指标[血氧饱和度(SaO_(2))、乳酸(Lac)、血钠(Na^(+))、血钾(K^(+))水平]和脑组织含水量;HE染色法观察大鼠脑皮质组织形态学;ELISA法检测血清PHD2、HIF-1α和血管内皮生长因子(VEGF)含量;Western blot法检测脑组织VEGF蛋白表达,实时荧光定量PCR法检测脑组织VEGFmRNA表达。结果:与空白组比较,模型组大鼠SaO_(2)和Na^(+)水平降低(P<0.05),Lac、K^(+)水平及脑组织含水量升高(P<0.05)。与模型组比较,砭贴组和药物组SaO_(2)水平升高(P<0.05),Lac、K^(+)水平及脑组织含水量降低(P<0.05);砭贴组Na+水平升高(P<0.05)。与砭贴组比较,砭贴抑制剂组SaO_(2)水平降低(P<0.05),Lac水平及脑组织含水量升高(P<0.05)。模型组大鼠脑皮质组织细胞疏松紊乱,皮质血管扩张,细胞明显肿胀;砭贴组和药物组缺氧损伤表现较轻,砭贴抑制剂组缺氧损伤较砭贴组明显。与空白组比较,模型组大鼠血清PHD2含量降低、HIF-1α含量升高(P<0.05),血清VEGF含量及脑组织VEGF蛋白和m RNA表达增加(P<0.05);与模型组比较,砭贴组和药物组血清PHD2含量升高、HIF-1α含量降低(P<0.05),血清VEGF含量及脑组织VEGF蛋白和mRNA表达降低(P<0.05);与砭贴组比较,砭贴抑制剂组血清PHD2含量降低、HIF-1α含量升高(P<0.05),血清VEGF含量及脑组织VEGF mRNA表达升高(P<0.05)。结论:砭贴“内关”“太渊”“人迎”可能通过调控血清PHD2/HIF-1α水平下调VEGF表达,减轻脑组织水肿、增强大鼠抗缺氧能力,从而达到预防高原脑损伤的目的。
Objective To observe the effect of Biantie(bian stone plaste)pretreatment on serum level of prolyl hydroxylase domain 2(PHD2)and hypoxia-inducible factor-1α(HIF-1α)in rats with acute hypobaric hypoxia induced-brain injury,and to explore the possible mechanism of Biantie on preventing brain injury at high altitude.Methods Forty-five male SD rats were randomly divided into a blank group,a model group,a Biantie group,a medication group and a Biantie+inhibitor group,9 rats in each group.The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at"Taiyuan"(LU 9),"Neiguan"(PC 6)and"Renying"(ST 9),2 h each time,once a day;the rats in the medication group were treated with intragastric administration of rhodiola capsule solution(280 mg/kg)for 14 d;the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine(DMOG)at a dose of 40 mg/kg 24 h before the establishment of the model.After the intervention,except for the blank group,the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model.The arterial blood-gas analysis indexes[blood oxygen saturation(SaO_(2)),lactic acid(Lac),blood sodium(Na^(+)),blood potassium(K^(+))]and brain water content were detected in each group;the histomorphology of cerebral cortex was observed by HE staining;the serum levels of PHD2 and HIF-1αas well as vascular endothelial growth factor(VEGF)were detected by ELISA;the VEGF protein expression in brain tissue was detected by Western blot;the VEGF m RNA expression in brain tissue was detected by real-time fluorescent quantitative PCR.Results Compared with the blank group,the levels of SaO_(2) and Na^(+)in the model group were decreased(P<0.05),while the levels of Lac and K^(+)as well as the water content of brain tissue were increased(P<0.05).Compared with the model group,the level of SaO_(2) in the Biantie group and the medication group was increased(P<0.05),while the levels of Lac,K^(+)and the water content of brain tissue were decreased(P<0.05);the level of Na^(+)in the Biantie group was increased(P<0.05).Compared with the Biantie group,the level of SaO_(2) in the Biantie+inhibitor group was decreased(P<0.05),and the level of Lac and the water content of brain tissue were increased(P<0.05).In the model group,the cortical tissue cells were loose and disordered,the cortical blood vessels were dilated,and the cells were obviously swollen;the anoxic injury in the Biantie group and the medication group was lighter,and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group.Compared with the blank group,the serum PHD2 content in the model group was decreased and the HIF-1αcontent was increased(P<0.05),and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased(P<0.05).Compared with the model group,the content of PHD2 in serum in the Biantie group and the medication group was increased(P<0.05),and the level of HIF-1αwas decreased(P<0.05),and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased(P<0.05).Compared with the Biantie group,the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1αlevel were increased(P<0.05),and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased(P<0.05).Conclusion Biantie at"Taiyuan"(LU 9),"Neiguan"(PC 6)and"Renying"(ST 9)could regulate serum PHD2/HIF-1αto down-regulate VEGF expression,reduce brain edema and enhance anti-hypoxia ability,so as to achieve the purpose of preventing brain injury at high altitude.
作者
李晓雅
吴春花
闫颖洁
王登辉
王梦杰
侯中伟
LI Xiao-ya;WU Chun-hua;YAN Ying-jie;WANG Deng-hui;WANG Meng-jie;HOU Zhong-wei(College of Acupuncture-Moxibustion and Tuina,Beijing University of CM,Beijing 100029,China)
出处
《中国针灸》
CAS
CSCD
北大核心
2022年第11期1278-1284,共7页
Chinese Acupuncture & Moxibustion
基金
国家社科基金特别委托项目:14@ZH001
北京中医药大学教育基金项目:1000062620191。
关键词
高原脑损伤
砭贴
急性低压低氧
脑组织损伤
脯氨酸羟化酶2
低氧诱导因子1Α
血管内皮生长因子
high-altitude brain injury
Biantie
acute hypobaric hypoxia
brain tissue injury
prolyl hydroxylase domain 2(PHD2)
hypoxia-inducible factor-1α(HIF-1α)
vascular endothelial growth factor(VEGF)
