铁皮石斛多糖调控JAK2/STAT5通路抑制非酒精性脂肪肝小鼠肝脏内质网应激作用分析

Effect of Dendrobium Dendrobium Polysaccharide on the Inhibition of Liver Endoplasmic Reticulum Stress in Mice with Nonalcoholic Fatty Liver by Regulating Jak2/Stat5 Pathway

目的 探讨分析铁皮石斛多糖调控JAK2/STAT5通路抑制非酒精性脂肪肝小鼠肝脏内质网应激作用。方法 将50只小鼠随机分为对照组、模型组、低剂量组(20μg/mL)、中剂量组(40μg/mL)及高剂量组(80μg/mL),每组10只,除对照组外,其余小鼠使用高脂饲料诱发脂肪肝模型,低、中、高剂量组小鼠分别使用不同剂量铁皮石斛灌胃。连续给药8周后,取各组小鼠肝组织样本进行HE染色,检测各组小鼠血清肝功能及血脂指标,并采用RT-qPCR法检测小鼠肝组织中JAK2、STAT5、GRP78、CHOP、Caspase 12、Bcl-2、Bax基因表达情况。结果 模型组及给药组小鼠体质量、肝脏重量以及肝脏指数均较对照组显著升高(P<0.05),而给药组小鼠体质量、肝脏重量以及肝脏指数均较模型组降低(P<0.05),且呈剂量依赖关系。模型组及给药组AST、ALT、TC、TG、LDL-C均较对照组显著升高(P<0.05),HDL-C较对照组显著降低(P<0.05),而给药组小鼠AST、ALT、TC、TG、LDL-C均较模型组降低(P<0.05),HDL-C较模型组升高(P<0.05),且呈剂量依赖关系。肝组织HE染色结果显示,模型组肝小叶结构出现严重破坏,可见大量脂肪空泡聚集,铁皮石斛多糖各组小鼠肝细胞可见明显地排列不整齐,脂肪空泡汇聚,较模型组有不同程度的改善。模型组及给药组小鼠肝组织JAK2、STAT5以及Bcl-2基因相对表达量显著降低(P<0.05),GRP78、CHOP、Caspase 12以及Bax基因相对表达量显著升高(P<0.05),各铁皮石斛多糖药物干预组JAK2、STAT5以及Bcl-2基因相对表达量显著升高(P<0.05),GRP78、CHOP、Caspase 12以及Bax基因相对表达量显著降低(P<0.05),且呈明显的剂量依赖性。结论 铁皮石斛多糖可有效改善非酒精性脂肪肝小鼠肝损伤,且疗效呈显著的剂量依赖,其机制可能与激活JAK2/STAT5通路抑制内质网应激有关。

Objective To investigate the inhibitory effect of Dendrobium officinale polysaccharide on the stress of liver endo-plasmic reticulum in mice with nonalcoholic fatty liver by regulating JAK2/STAT5 pathway.Methods Fifty mice were randomLy divided into control group,model group,low-dose group(20μg/mL),medium-dose group(4Oμg/mL)and high-dose group(80μg/mL),with 10 mice in each group.Except for the control group,the other mice were induced with fatty liver model by high-fat diet,and the mice in the low-dose,medium-dose and high-dose groups were given different doses of Dendrobium offici-nale by gavage.After 8 weeks of continuous administration,liver tissue samples of mice in each group were taken for HE staining to detect serum liver function and blood lipid indexes of mice in each group,and the gene expressions of JAK2,STAT5,GRP78,CHOP,Caspase 12,Bcl-2 and Bax in liver tissue of mice were detected by RT-qPCR.Result The body weight,liver weight and liver index of mice in the model group and the various dose groups were significantly increased compared with the control group(P<0.05),while the body weight,liver weight and liver index of mice in the treatment group were significantly decreased com-pared with the model group(P<O.05),and showed a dose-dependent relationship.The AST,ALT,TC,TG,LDL-C of mice in the model group and the various dose groups were significantly increased compared with the control group(P<0.05),while the HDL-C of mice in the various dose groups were significantly decreased compared with the model group(P<0.05),and the HDL-C of mice in the various dose groups was significantly increased compared with the model group(P<0.05),and showed a dose-dependent relationship.The HE staining results of liver tissue showed that the structure of hepatic lobules was seriously damaged in the model group,and a large number of fat vacuoles were gathered.The hepatic cells of mice in the D.candidum polysaccharide groups showed obvious disordered arrangement and fat vacuoles aggregation,which were improved to varying degrees compared with the model group.The relative expression levels of JAK2,STAT5 and Bcl-2 genes in the liver tissue of mice in the model group and the various dose groups were significantly decreased(P<0.05),while the relative expression levels of CRP78,CHOP,Caspase 12 and Bax genes were significantly increased(P<0.05).The relative expression levels of JAK2,STAT5 and Bcl-2 genes in the liver tissue of mice in the D.candidum polysaccharide drug intervention groups were significantly increased(P<0.05),while the relative expression levels of CRP78,CHOP,Caspase 12 and Bax genes were significantly decreased(P<0.05),and showed an obvious dose-dependent relationship.Conclusion Dendrobium dendrobium polysaccharide can effectively improve liver injury in mice with nonalcoholic fatty liver,and the treatment is significantly dose-dependent,which may be related to the activation of JAK2/STAT5 pathway to inhibit endoplasmic reticulum stress.