苓桂术甘汤对急性心肌梗死后大鼠肠黏膜屏障损伤的保护作用研究

Protective Effect of Linggui Zhugan Decoction Against Intestinal Mucosal Barrier Injury in Rats After Acute Myocardial Infarction

目的观察苓桂术甘汤对急性心肌梗死(acute myocardial infarction,AMI)后大鼠肠道黏膜屏障损伤的保护作用。方法采用冠状动脉结扎法复制AMI大鼠模型,将模型大鼠随机分别为模型组,苓桂术甘汤低剂量(2.1 g/kg)、中剂量(4.2 g/kg)、高剂量(8.4 g/kg)组,另设假手术组,连续处理4周,采用苏木精-伊红染色法观察心脏和回肠组织病理学变化,ELISA法检测D-乳酸、脂多糖(lipopolysaccharide,LPS)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)和白细胞介素-1β(interleukin-1β,IL-1β)含量,Western blot法和RT-PCR法检测回肠组织闭合蛋白(Occludin)、带状闭合蛋白(zonula occludens-1,ZO-1)及其mRNA表达水平。结果与假手术组比较,模型组大鼠心脏出现明显的心肌损伤及炎症细胞浸润,回肠组织发生肠黏膜脱落,绒毛和腺体稀疏,炎症细胞浸润等病理学变化,血浆D-乳酸和LPS含量升高,回肠组织Occludin和ZO-1蛋白及mRNA表达水平下调,回肠组织TNF-α、IL-6、IL-1β及心脏组织TNF-α含量增加(P<0.05);与模型组比较,苓桂术甘汤各剂量组均可改善AMI后大鼠心肌和肠道组织损伤,降低血浆D-乳酸和LPS含量,上调肠组织Occludin和ZO-1蛋白及其mRNA表达水平,降低回肠组织TNF-α、IL-6、IL-1β及心脏组织TNF-α的含量(P<0.05)。结论苓桂术甘汤改善AMI后大鼠肠黏膜屏障的损伤与调节肠道通透性、降低肠道炎症反应有关。

Objective To investigate the protective effect of Linggui Zhugan Decoction against intestinal mucosal barrier injury in rats after acute myocardial infarction(AMI).Methods Coronary artery ligation was performed to establish a rat model of AMI,and the model rats were randomly divided into model group and low-,middle-,and high-dose(2.1,4.2,and 8.4 g/kg)Linggui Zhugan Decoction groups.A sham-operation group was established,and all groups were treated for 4 consecutive weeks.HE staining was used to observe the pathological changes of the heart and the ileal tissue;ELISA was used to measure the content of D-lactate,lipopolysaccharide(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β);Western blot and RT-PCR were used to measure the protein and mRNA expression levels of occludin and zonula occluden-1(ZO-1)in ileal tissue.Results Compared with the sham-operation group,the model group had marked pathological changes(including marked myocardial injury and inflammatory cell infiltration in the heart and exfoliation of intestinal mucosa,sparse villi and glands,and inflammatory cell infiltration in ileal tissue),significant increases in plasma levels of D-lactate and LPS,significant reductions in the protein and mRNA expression levels of ZO-1 and occludin in ileal tissue,and significant increases in the levels of TNF-α,IL-6,and IL-1βin ileal tissue and the level of TNF-αin heart tissue(P<0.05).Compared with the model group,Linggui Zhugan Decoction groups had marked improvement in myocardial and intestinal injury after AMI,significant reductions in the plasma levels of D-lactate and LPS,significant increases in the protein and mRNA expression levels of ZO-1 and occludin in intestinal tissue,and significant reductions in the levels of TNF-α,IL-6,and IL-1βin ileal tissue and the level of TNF-αin heart tissue(P<0.05).Conclusion Linggui Zhugan Decoction improves intestinal mucosal barrier injury in rats after AMI,possibly by regulating intestinal permeability and reducing intestinal inflammatory response.