止痛顺气胶囊对慢性萎缩性胃炎模型大鼠JAK/STAT信号通路的影响
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篇名: 止痛顺气胶囊对慢性萎缩性胃炎模型大鼠JAK/STAT信号通路的影响
TITLE: Effects of Zhitong Shunqi Capsule on JAK/STAT Signaling Pathway of Chronic Atrophic Gastritis Model Rats
摘要: 目的:研究止痛顺气胶囊对慢性萎缩性胃炎(CAG)模型大鼠酪氨酸激酶/信号转导子和转录激活子(JAK/STAT)信号通路的影响,为阐明其改善CAG的作用机制提供参考。方法:将60只SD大鼠随机分为空白组、模型组、阳性对照组[维酶素,0.09g/(kg·d)]和止痛顺气胶囊低、中、高剂量组[0.75、1.5、3g/(kg·d)],每组10只。除空白组外,其余各组大鼠均采用N-甲基-N′-硝基-N-亚硝基胍自由饮用联合饥饱失常的方法复制CAG模型。造模结束后,各给药组大鼠灌胃相应药物,空白组和模型组大鼠灌胃等体积水,连续给药28d。给药结束后,采用酶联免疫吸附法测定大鼠血清中白细胞介素1β(IL-1β)、IL-6水平,采用苏木精-伊红染色法观察各组大鼠的胃黏膜组织病理学变化,分别采用实时荧光定量-聚合酶链式反应法和Westernblotting法检测大鼠胃黏膜组织中JAK1、STAT3、细胞因子信号传导抑制因子(SOCS-3)、c-Myc的mRNA及其蛋白表达水平。结果:与空白组比较,模型组大鼠胃黏膜可见排列稀疏不整齐的腺体,以及着色深染的细胞核;血清中IL-1β、IL-6水平以及胃黏膜组织中JAK1、STAT3、c-MycmRNA及其蛋白表达水平显著升高(P<0.05),胃黏膜组织中SOCS-3mRNA及其蛋白表达水平显著降低(P<0.05)。与模型组比较,各给药组大鼠胃黏膜腺体排列较整齐,染色较深的核细胞数较少;止痛顺气胶囊低剂量组大鼠血清中IL-6水平和胃黏膜组织中c-MycmRNA表达水平显著降低(P<0.05),SOCS-3蛋白表达水平显著升高(P<0.05);止痛顺气胶囊中剂量组大鼠血清中IL-1β、IL-6水平和胃黏膜组织中JAK1、STAT3、c-MycmRNA表达水平以及胃黏膜组织中JAK1蛋白表达水平显著降低(P<0.05),胃黏膜组织中SOCS-3mRNA及其蛋白表达水平显著升高(P<0.05);阳性对照组和止痛顺气胶囊高剂量组大鼠上述指标水平均显著改善(P<0.05)。与阳性对照组比较,止痛顺气胶囊高剂量组胃黏膜组织中STAT3mRNA及其蛋白表达水平显著降低(P<0.05)。结论:止痛顺气胶囊对CAG模型大鼠具有一定的改善作用;其机制可能与下调JAK1、STAT3、c-MycmRNA及其蛋白表达,上调SOCS-3mRNA及其蛋白表达有关。
ABSTRACT: OBJECTIVE:To stud y the effects of Zhitong shunqi capsule on JAK/STAT signaling pathway of chronic atrophic gastritis(CAG)model rats ,and to provide reference for clarifying its mechanism of improving CAG. METHODS :Totally 60 SD rats were randomly divided into blank group ,model group ,positive control group [vitacoenzyme ,0.09 g/(kg·d)],Zhitong shunqi capsule low-dose ,medium-dose and high-dose groups [ 0.75,1.5,3 g/(kg·d)],with 10 rats in each group. Except for blank group,other groups were given N-methyl-N′-nitro-N-nitrosoguanidine freely drinking combined with abnormal ingestion method to induce CAG model. After end of modeling ,administration groups were given relevant medicine intragastrically ,blank group and model group were given constant volume of water intragastrically ,for consecutive 28 d. After end of medication ,ELISA method was used to determine the serum levels of IL- 1β and IL-6;the gastric mucosa tissue pathologic change was observed by HE staining;mRNA and protein expressions of JAK 1,STAT3,SOCS-3 and c-Myc in gastric mucosa tissue were detected by real-time PCR and Western blotting assay. RESULTS :Compared with blank group ,the sparse and irregular glands with deep staining cell nucleus could be seen in the gastric mucosa of rats in model group ;serum levels of IL- 1 β and IL-6,mRNA and protein expressions of JAK 1,STAT3 and c-Myc in gastric mucosa tissue were increased significantly (P<0.05),while mRNA and protein expression of SOCS- 3 in gastric mucosa tissue were decreased significantly (P<0.05). Compared with model group , glandular arrangement of gastric mucosa was more orderly and the number of heavy stained cells was less in administration groups;serum level of IL- 6 and mRNA expression of c-Myc in gastric mucosa of rats was decreased significantly in Zhitong shunqi capsule low-dose group (P<0.05),while the protein expression of SOCS- 3 was increased significantly (P<0.05); serum levels of IL- 1β and IL-6,mRNA expressions of JAK 1,STAT3 and c-Myc in gastric mucosa tissue ,protein expression of JAK1 were decreased significantly in Zhitong shunqi capsule medium-dose group (P<0.05),while mRNA and protein expression of SOCS- 3 was increased significantly in gastric mucosa tissue (P<0.05);above indexes were improved significantly in positive control group and Zhitong shunqi capsule high-dose group (P<0.05). Compared with positive control group ,mRNA and protein expression of STAT 3 in gastric mucosa tissue were decreased significantly in Zhitong shunqi capsule high-dose group (P<0.05). CONCLUSIONS:Zhitong shunqi capsule can improve CAG model rat to certain extent ,the mechanism of which may be associated with the down-regulation of mRNA and protein of JAK 1,STAT3 and c-Myc ,and up-regulation of mRNA and protein of SOCS-3.
期刊: 2020年第31卷第11期
作者: 孙玉霞,梁波,文黛薇,黄贤元
AUTHORS: SUN Yuxia,LIANG Bo,WEN Daiwei ,HUANG Xianyuan
关键字: 止痛顺气胶囊;慢性萎缩性胃炎;胃黏膜;酪氨酸激酶/信号转导子和转录激活子信号通路;大鼠
KEYWORDS: Zhitong shunqi capsule ;Chronic atrophic gastritis ;Gastric mucosa ;JAK/STAT signaling pathway ;Rat
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