摘要
目的观察大黄对内毒素性肠损伤大鼠PTEN/PI3K/Akt信号通路的影响,探讨其作用机制。方法将30只雄性Wistar大鼠随机分为正常组、模型组、地塞米松组和大黄低、高剂量组,每组6只。各给药组造模前给予相应药液灌胃,连续5 d,每日1次。第5日给药后2 h,除正常组外各组大鼠尾静脉注射脂多糖制备肠损伤模型。造模7h后取材,光镜下观察大鼠肠组织病理学改变,免疫组化检测PTEN、PI3K、Akt、mTOR蛋白的表达,Western blot检测PI3K、p-mTOR蛋白的表达。结果模型组大鼠肠壁黏膜层广泛变性坏死,大量肉芽组织增生;地塞米松组和大黄低、高剂量组病理学改变较模型组减轻。免疫组化结果显示,与正常组比较,模型组大鼠肠组织PTEN蛋白表达显著降低(P<0.001),PI3K、Akt蛋白表达显著升高(P<0.001,P<0.01);与模型组比较,大黄高剂量组大鼠肠组织PTEN蛋白表达显著升高(P<0.01),大黄低、高剂量组PI3K、Akt蛋白表达显著降低(P<0.001)。Western blot结果显示,与模型组比较,地塞米松组和大黄低、高剂量组大鼠肠组织PI3K、p-mTOR蛋白表达显著降低(P<0.05)。结论大黄对内毒素性肠损伤大鼠具有保护作用,其机制可能与上调肠组织PTEN和下调PI3K、Akt、p-mTOR的表达,抑制PI3K/Akt信号通路有关。
Objective To investigate the effect of Rhei Radix et Rhizoma on PTEN/PI3K/Akt signaling pathway in rats with endotoxin-induced intestinal injury;To discuss its mechanism.Methods Totally 30 male Wistar rats were randomly divided into normal group,model group,dexamethasone group,Rhei Radix et Rhizoma low-,high-dosage groups,with 6 rats in each group.Before modeling,each administration group was given the corresponding drug solution by gavage for 5 consecutive days,once a day.On the 5 th day,2 hours after the administration,rats in all groups except the normal group were injected with lipopolysaccharide through the tail vein to prepare intestinal injury models.Samples were obtained 7 h after modeling.The pathological changes of the intestinal tissues of rats were observed under light microscope.The protein expressions of PTEN,PI3K,Akt and mTOR were detected by immunohistochemistry,and the protein expressions of PI3K and p-mTOR were detected by Western blot.Results In the model group,the mucosal layer of the intestinal was extensively degenerated and necrotic,and a large amount of granulation tissue proliferated.The pathological changes in the dexamethasone group,Rhei Radix et Rhizoma lowand high-dosage groups were relieved compared with the model group.The results of immunohistochemistry showed that,compared with the normal group,the positive area of PTEN protein expressions in the intestinal tissue of the model group was significantly reduced(P<0.001),and the positive area of PI3K and Akt protein expressions significantly increased(P<0.001,P<0.01);compared with the model group,the positive area of PTEN protein expression in the intestinal tissue of the Rhei Radix et Rhizoma high-dosage group significantly increased(P<0.01),and the positive area of PI3K and Akt protein expression in the Rhei Radix et Rhizoma low-,high-dosage groups significantly decreased(P<0.001).Western blot results showed that,compared with the model group,the expressions of PI3K and p-mTOR in the intestinal tissue of the dexamethasone group and Rhei Radix et Rhizoma low-,high-dosage groups were significantly reduced(P<0.05).Conclusion Rhei Radix et Rhizoma has a protective effect on rats with endotoxin-induced intestinal injury,which may be related to the inhibition of PI3K/Akt signaling pathway by up-regulating PTEN and down-regulating the expressions of PI3K,Akt and p-mTOR proteins in intestinal tissue.
作者
汪顺
单聪
朱华贺
谭波
李小茜
杨爱东
WANG Shun;SHAN Cong;ZHU Huahe;TAN Bo;LI Xiaoqian;YANG Aidong(College of Basic Medical Science,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2021年第5期65-69,共5页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家重点研发计划(2018YFC1704102、2018YFC1704100)
国家自然科学基金面上项目(81673855)
上海市进一步加快中医药事业发展三年行动计划[ZY(2018-2020)-CCCX-2001-01]
上海中医药大学中医临床基础学科(A1-Z193020109)。
