基于JAK2/STAT3信号通路探究半夏泻心汤对慢性萎缩性胃炎大鼠的影响

The Effect of Banxia Xiexin Decoction(半夏泻心汤)on Chronic Atrophic Gastritis Rats Based on JAK2/STAT3 Signaling Pathway

目的:探讨半夏泻心汤对慢性萎缩性胃炎大鼠的保护作用及其对Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)通路的影响。方法:72只大鼠随机选取12只作为空白组,其余大鼠采用N-甲基-N-硝基-N-亚硝基胍(MNNG)溶液联合饥饱失常饮食控制法及雷尼替丁灌胃法建立慢性萎缩性胃炎大鼠模型,造模共12周。将造模成功的大鼠随机分为模型组、维酶素组、半夏泻心汤高剂量组、半夏泻心汤中剂量组、半夏泻心汤低剂量组。各给药组大鼠灌胃给予相应药物,空白组及模型组大鼠灌胃给予等体积生理盐水,1次/d,连续6周。HE染色观察大鼠胃黏膜组织病理变化;免疫组化检测Bax、Bcl-2蛋白表达;ELISA法检测大鼠胃组织中SOD、CAT、GSH-Px、MDA水平及TNF-α、IL-1β、IL-6水平;Western blotting法检测胃组织JAK2、p-JAK2、STAT3、p-STAT3蛋白表达水平。结果:与空白组比较,模型组大鼠胃黏膜变薄,上皮细胞及腺体排列紊乱,腺体数目明显减少,可见大量炎症细胞浸润,SOD、CAT、GSH-Px水平及胃组织Bax蛋白表达均明显降低(P<0.01);TNF-α、IL-1β、IL-6、MDA水平,Bcl-2蛋白表达,以及p-JAK2、p-STAT3蛋白相对表达量均明显升高(P<0.01)。与模型组比较,维酶素组和半夏泻心汤高、中、低剂量组大鼠胃黏膜腺体排列比较规整,各层结构较为正常,可见少量腺体变形萎缩及炎症细胞浸润;SOD、CAT、GSH-Px水平及胃组织Bax蛋白表达均明显升高(P<0.05);TNF-α、IL-1β、IL-6、MDA水平,Bcl-2蛋白表达,以及p-JAK2、p-STAT3蛋白相对表达量均明显降低(P<0.05);6组大鼠胃组织JAK2、STAT3蛋白相对表达量比较,差异无统计学意义(P>0.05)。结论:半夏泻心汤可能通过调节JAK2/STAT3通路中相关因子和蛋白的表达来抑制慢性萎缩性胃炎的进展,从而发挥胃组织保护作用。

Objective:To investigate the protective effect of Banxia Xiexin decoction on rats with chronic atrophic gastritis and its effect on the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:Totally 12 rats were randomly selected from 72 rats as the blank group,and the rest were given N-methyl-N-nitro-N-nitrosoguanidine(MNNG)solution combined with hunger-satiety disorder diet control and ranitidine gavage for 12 weeks,to establish rat model of chronic atrophic gastritis.The rats with successful modeling were randomly divided into model group,vitacoenzyme group,high dose Banxia Xiexin decoction group,medium dose Banxia Xiexin decoction group and low dose Banxia Xiexin decoction group.The rats in each administration group were given the corresponding drugs by gavage,and the rats in the blank group and model group were given the same volume of normal saline by gavage, once a day for 6 weeks. The histopathological changes of rat gastric mucosa were observed by HE staining. Bax and Bcl-2 protein expression were detected by immunohistochemistry. The SOD, CAT, GSH-Px and MDA levels as well as TNF-α, IL-1β and IL-6 levels were detected by ELISA. JAK2, p-JAK2, STAT3 and p-STAT3 protein expression levels were detected by Western blotting. Results: Compared with the blank group, the gastric mucosa of rats in the model group was thinner, with disorganized epithelial cells and glands, and the number of glands was significantly reduced. A large number of inflammatory infiltrates could be seen in model group. The levels of SOD, CAT, GSH-Px and the expression of Bax protein in gastric tissues were significantly reduced (P<0.01), while the levels of TNF-α, IL-1β, IL-6 and MDA, as well as the expression of Bcl-2, p-JAK2 and p-STAT3 protein were significantly increased in model group (P<0.01). Compared with the model group, the gastric mucosal glands of the rats in the vitacoenzyme group and the high, medium and low dose Banxia Xiexin decoction groups were arranged regularly. The structure of each layer was relatively normal, and a small amount of gland deformation and atrophy and inflammatory cells were observed in vitacoenzyme group and the high, medium and low dose Banxia Xiexin decoction groups. The levels of SOD, CAT, GSH-Px and the expression of Bax protein in gastric tissues were significantly increased (P<0.01), while the levels of TNF-α, IL-1β, IL-6 and MDA, as well as the expression of Bcl-2, p-JAK2 and p-STAT3 protein were significantly reduced in vitacoenzyme group and high, medium and low dose Banxia Xiexin decoction groups (P<0.01). There was no significant difference in JAK2 and STAT3 protein in gastric tissues among the 6 groups (P>0.05). Conclusion: Banxia Xiexin decoction may inhibit the progression of chronic atrophic gastritis by regulating the expression of related factors and proteins in the JAK2/STAT3 pathway, thus play a protective role in gastric tissue.