摘要
目的:探讨丹参素经磷脂酰肌醇3-激酶(PI3K)/丝氨酸/苏氨酸蛋白激酶(Akt)/促凋亡基因(Bax)信号通路对脓毒症大鼠脑损伤的改善作用。方法:100只SD大鼠随机分为5组:假手术组、模型组、乌司他丁组(20 mg·kg^-1)、丹参素低、高剂量组(40,80 mg·kg^-1),每组20只。除假手术组外,其余各组建立脓毒症模型。乌司他丁组、丹参素低、高剂量组给予相应药物灌胃,假手术组及模型组给予等体积的生理盐水,1次/d,持续给药7 d。实验结束后,评估大鼠神经功能,观察大鼠海马神经元病理结构,测定大鼠海马组织PI3K、Akt、Bax mRNA和蛋白表达水平。结果:与假手术组比较,模型组Basso-Beattie-Bresnahan(BBB)评分、经过原平台位置的次数、原平台象限停留时间、PI3K、Akt mRNA和蛋白表达水平明显降低,逃避潜伏期、Bax mRNA和蛋白表达水平明显升高(P<0.05)。与模型组比较,乌司他丁组和丹参素低、高剂量组BBB评分、经过原平台位置的次数、原平台象限停留时间、PI3K、Akt mRNA和蛋白表达水平明显升高,逃避潜伏期、Bax mRNA和蛋白表达水平明显降低(P<0.05)。与乌司他丁组比较,丹参素低剂量组各指标差异有统计学意义(P<0.05),高剂量组与其作用相似(P>0.05)。结论:丹参素可减轻脓毒症大鼠脑损伤,其机制与丹参素激活PI3K/Akt信号通路进而抑制Bax的表达有关。
Objective:To investigate the effect of tanshinol on brain injury in sepsis rats via PI3K/Akt/Bax signal pathway.Methods:Totally 100 SD rats were randomly divided into 5 groups:sham operation group,model group,ulinastatin group(20 mg·kg^-1),and tanshinol low and high dose groups(40 and 80 mg·kg^-1)with 20 in each group.Excpet the sham operation group,the other groups established the sepsis model.After the model was established successfully,ulinastatin group,tanshinol low and high dose groups were given corresponding drug by gavage,and the normal control group and the model group were given equal volume of normal saline,once a day,and with continuous administration for 7 days.At the end of experiment,the neurological function of rats were evaluated,the pathological structure of hippocampal neurons was observed in rats,and the expressions of PI3K,Akt,Bax mRNA and protein in hippocampus were evaluated by real time fluorescence quantitative PCR(RT-PCR)and Western blot.Results:Compared with those in the sham operation group,the Basso-Beattie-Bresnahan(BBB)score,number of times of passing through the original platform position,time of staying in the original platform quadrant,and PI3K,Akt mRNA and protein expression levels in the model group were significantly reduced,and the escape latency,and the Bax mRNA and protein expression levels were significantly increased(P<0.05).Compared with those in the model group,the BBB score,times of passing through the original platform position,time of staying in the original platform quadrant,and PI3K,Akt mRNA and protein expression levels in ulinastatin group and tanshinol low and high dose groups were significantly increased,and the escape latency,and the levels of Bax mRNA and protein were significantly decreased(P<0.05).Compared with those in ulinastatin group,the indices of tanshinol low dose group had statistically significant differences(P<0.05),and the effects of the high dose group were similar.Conclusion:Tanshinol can reduce brain damage in sepsis rats,and its mechanism is related to the activation of PI3K/Akt signaling pathway by tanshinol to inhibit the expression of Bax.
作者
张宇
周灵敏
邵飞飞
管智慧
Zhang Yu;Zhou Lingmin;Shao Feifei;Guan Zhihui(Department of Critical Medicine,Taizhou First People's Hospital,Zhejiang Taizhou 318020,China)
出处
《中国药师》
CAS
2020年第10期1926-1930,共5页
China Pharmacist
