棘球蚴通过mTOR途径抑制糖酵解的研究

Echinococcus infection inhibits glycolysis through mTOR pathway

目的观察棘球蚴感染后,mTOR途径对T细胞糖酵解的影响。方法将Balb/c小鼠随机分为对照组、感染组和抑制剂组。感染组和抑制剂组肝被膜下注射原头蚴,对照组注射等体积的PBS,抑制剂组从第2天起每日腹腔注射雷帕霉素(1.25 mg/kg)。分别于感染后15、30和70 d,收集外周血和脾脏,qRT-PCR检测糖酵解相关转录因子的mRNA表达,Western blot检测mTOR途径下游分子的蛋白表达。结果与对照组比较,感染组中mTOR途径下游分子HIF-1α、P-p70S6和P-4EBP-1的蛋白表达降低(P<0.05),糖酵解相关转录因子HK3、PKM2、LDHA和MCT4的mRNA表达降低(P<0.05),加入雷帕霉素抑制mTOR途径后,糖酵解相关转录因子HK3、PKM2、LDHA和MCT4的mRNA表达进一步降低(P<0.001)。结论棘球蚴感染通过mTOR途径抑制了T细胞的糖酵解代谢。

Objective To observe the effect of mTOR pathway on glycolysis of T cells after Echinococcus granulosus infection.Methods Balb/c mice were randomly divided into control group,infection group and inhibitor group.In the infection group and inhibitor group,protoscolex was injected under the liver capsule,the control group was injected with an equal volume of PBS,and the inhibitor group was intraperitoneally injected with rapamycin(1.25 mg/kg)daily from the next day.At 15,30,and 70 days after infection,peripheral blood and spleen were collected,qRT-PCR was used to detect the mRNA expression of metabolic enzymes,and Western blot was used to detect the protein expression of the mTOR signaling pathway.Results Compared with the control group,the protein expression of HIF-1α,P-p70S6 and P-4EBP-1 downstream of the mTOR pathway in the infected group decreased(P<0.05),and the mRNA expression of glycolysis-related transcription factors HK3,PKM2,LDHA and MCT4 decreased(P<0.05).After rapamycin inhibited the mTOR pathway,the mRNA expression of glycolysis-related transcription factors HK3,PKM2,LDHA and MCT4 were further reduced(P<0.001).Conclusion Echinococcus infection inhibits glycolytic activity in T cells through the mTOR pathway.