黄连素对阿尔兹海默症大鼠Th17、Treg亚群比例及脑组织炎性细胞因子的影响

Effects of berberine on Th17,Treg subsets and inflammatory cytokines in brain tissue in rats with Alzheimer's disease

目的探究黄连素对阿尔兹海默症大鼠外周血辅助性T细胞(T helper cell,Th)17、调节性T细胞(regulatory T-cell,Treg)亚群比例,以及脑组织炎性细胞因子水平的影响。方法大鼠分为假手术组、模型组、黄连素组,除假手术组外,其余各组采用腹腔注射D-半乳糖联合Aβ25-35海马注射的方法建立阿尔兹海默症大鼠模型,药物干预4周后,留取标本,流式细胞技术检测两组大鼠外周血中Th17、Treg细胞比例,实时荧光定量PCR检测两组大鼠海马组织炎性细胞因子白细胞介素(interleukin,IL)-1β、IL-6、IL-17、IL-22、肿瘤坏死因子(tumor necrosis factor,TNF)-α、转化生长因子(transforming growth factor,TGF)-βmRNA转录水平。结果(1)与假手术组相比,模型组Th17、Treg细胞比例升高(P<0.05),与模型组相比,黄连素组大鼠外周Th17细胞比例降低(P<0.05);(2)与假手术组相比,模型组大鼠海马组织促炎性细胞因子IL-1β、IL-6、IL-17、IL-22、TNF-α转录水平均显著升高(P<0.01),抑炎性细胞因子TGF-β转录水平显著降低(P<0.01);与模型组相比,IL-1β、IL-6、IL-17、TNF-α转录水平均降低(P<0.05),TGF-β转录水平升高(P<0.05)。结论黄连素能降低阿尔兹海默症大鼠外周血Th17亚群比例,减轻脑组织内炎性反应。

Objective To explore the effect of berberine on the proportion of helper T cell 17(Th17),regulatory T-cell(Treg)subsets and inflammatory cytokines in brain tissue of rats with Alzheimer’s disease.Methods The rats were divided into sham operation group,model group and berberine group.Except sham operation group,the other groups were injected intraperitoneally with D-galactose and Aβ25-35 to establish model rats with Alzheimer’s disease.After 4 weeks of drug intervention,the samples were taken to detect the Th17,Treg cell proportion in peripheral blood with flow cytometry,the mRNA expression levels of IL-1β,IL-6,IL-17,IL-22,TNF-αand TGF-βin hippocampus tissue.Results Compared with the sham operation group,the ratio of Th17 and Treg cells in the model group increased(P<0.05),the transcription levels of IL-1β,IL-6,IL-17,TNF-αand IL-22 in hippocampus tissue increased significantly(P<0.01),and the transcription levels of TGF-βmRNA decreased significantly(P<0.01).Compared with the model group,the ratio of peripheral Th17 cells in berberine group decreased(P<0.05),the transcription levels of IL-1β,IL-6,IL-17 and TNF-αdecreased(P<0.01,P<0.05),and the transcription level of TGF-βmRNA increased(P<0.05).Conclusion Berberine can lower the proportion of Th17 subsets in peripheral blood of rats with Alzheimer’s disease and reduce the inflammatory response of brain tissue.