大鼠肝纤维化病理过程中肝组织SHP2表达与在体肝星状细胞凋亡的关系

肝脏 ›› 2022, Vol. 27 ›› Issue (4): 451-454.

大鼠肝纤维化病理过程中肝组织SHP2表达与在体肝星状细胞凋亡的关系

郝礼森, 杨小师, 张朋垒, 陈盼盼, 展宗媛, 何宇, 苗笑佳

063000 河北唐山华北理工大学附属医院消化内科(郝礼森,杨小师,张朋垒,陈盼盼,展宗媛,何宇,苗笑佳);青岛市第六人民医院(张朋垒)

收稿日期:2021-08-14 出版日期:2022-04-30 发布日期:2022-06-02
基金资助:
河北省自然科学基金资助项目(H2018209366)

The association between SHP2 expression and hepatic stellate cells apoptosis in rat liver tissues in vivo during the pathologic process of hepatic fibrogenesis

HAO Li-sen¹, YANG Xiao-shi¹, ZHANG Peng-lei^1,2, CHEN Pan-pan¹, ZHAN Zong-yuan¹, HE Yu¹, MIAO Xiao-jia¹

1. Department of Gastroenterology, the Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China;
2. The Sixth Hospital of Qingdao City, Shandong 266000, China

Received:2021-08-14 Online:2022-04-30 Published:2022-06-02

摘要/Abstract

摘要： 目的探讨大鼠肝纤维化病理过程中肝组织含SH2结构域的蛋白酪氨酸磷酸酶2 (SHP2)表达与在体肝星状细胞 (HSC)凋亡的关系。方法将50只健康雄性SD大鼠随机分为对照组(10只)、模型组(40只),采用腹腔注射四氯化碳法建立大鼠肝纤维化模型,Masson三色染色及HE染色测定大鼠肝组织的病理学变化,α-平滑肌肌动蛋白 (α-SMA)免疫组织化学及末段脱氧核苷酸转移酶介导的脱氧三磷酸尿苷缺口末段标记(TUNEL)双重染色测定在体活化HSC凋亡,免疫组织化学染色测定大鼠肝组织SHP2表达。结果免疫组织化学染色显示,与对照组大鼠肝组织SHP2阳性表达积分光密度值 (IOD)(0.19±0.01)比较,造模不同时间(2、4、6、8周)大鼠肝组织SHP2阳性表达IOD (0.23±0.01、0.27±0.01、0.30±0.01、0.33±0.01)显著升高(P<0.05),并随着造模时间的延长逐渐增加(P<0.05)。α-SMA免疫组织化学及TUNEL双重染色检测显示,正常大鼠肝组织中几乎见不到HSC凋亡,模型组大鼠随着肝纤维化的加重,肝组织中活化HSC与凋亡HSC均增加,但造模不同时间(2、4、6、8周)大鼠肝组织中肝星状细胞的凋亡指数(47%±1%、41%±2%、35%±1%、29%±1%)却逐渐减少(P<0.05)。结论在四氯化碳诱导的大鼠肝纤维化病理过程中,纤维化大鼠肝组织SHP2表达与在体HSC的凋亡呈显著负相关。

关键词: 含SH2结构域的蛋白酪氨酸磷酸酶2, 肝纤维化, 肝星状细胞, 细胞凋亡

Abstract: Objective To investigate the association between SHP2 expression and hepatic stellate cells (HSC) apoptosis in rats liver tissues in vivo during the pathologic process of hepatic fibrogenesis.Methods 50 healthy male SD rats were randomly divided into a control group (n=10) and a model group (n=40). Rat model of hepatic fibrogenesis was established by intraperitoneal injection of carbon tetrachloride (CCl4). Masson's trichrome and Hematoxylin and eosin (HE) staining were used for the histological analysis of the changes in liver tissues. The expression of SHP2 in hepatic tissues was analyzed by immunohistochemical staining. Dual staining of alpha-smooth muscle action (α-SMA) for HSC and TUNEL for apoptotic cells was used for analyzing the apoptotic indexes of HSC in the fibrogenic liver tissues.Results By immunohistochemical staining, it was demonstrated that the integral optical density (IOD) of SHP2 (0.19±0.01) in the liver tissues of the control group was lower than those of 0.23±0.01, 0.27±0.01, 0.30±0.01, 0.33±0.01 in the fibrogenic liver tissues of the model groups collected at 2, 4, 6, 8 weeks post CCl4 administration, with a notably increasing trend (P<0.05). Dual staining of α-SMA and TUNEL demonstrated that there were few apoptotic HSC in liver tissues of the control group, whereas both of the apoptotic HSC and the activated HSC coexisted in fibrogenic liver tissues. The apoptotic indexes of HSC in rats liver tissues at 2, 4, 6, and 8 weeks post CCl4 administration were 47%±1%, 41%±2%, 35%±1% and 29%±1%, respectively, showing a gradually lowering trend (P<0.05).Conclusion During the pathological process of rat liver fibrogenesis, there is an negative correlation between the expression level of SHP2 and the HSC apoptosis in liver tissues in vivo.

Key words: SHP2, Hepatic fibrosis, Hepatic stellate cells, Apoptosis

郝礼森, 杨小师, 张朋垒, 陈盼盼, 展宗媛, 何宇, 苗笑佳. 大鼠肝纤维化病理过程中肝组织SHP2表达与在体肝星状细胞凋亡的关系[J]. 肝脏, 2022, 27(4): 451-454.

HAO Li-sen, YANG Xiao-shi, ZHANG Peng-lei, CHEN Pan-pan, ZHAN Zong-yuan, HE Yu, MIAO Xiao-jia. The association between SHP2 expression and hepatic stellate cells apoptosis in rat liver tissues in vivo during the pathologic process of hepatic fibrogenesis[J]. Chinese Hepatolgy, 2022, 27(4): 451-454.

参考文献

[1] Huang WQ, Lin Q, Zhuang X, et al. Structure, function, and pathogenesis of SHP2 in developmental disorders and tumorigenesis. Curr Cancer Drug Targets, 2014, 14: 567-588.
[2] Chan R J, Feng GS. PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase . Blood, 2007, 109: 862-867.
[3] Zhang J, Zhang F, Niu R. Functions of SHP-2 in cancer . J Cell Mol Med, 2015, 19: 2075-2083.
[4] Shen D, Chen W, Zhu J, et al. Therapeutic potential of targeting SHP2 in human developmental disorders and cancers. Eur J Med Chem, 2020, 190:112117.
[5] Kang HJ, Chung DH, Sung CO, et al. SHP2 is induced by the HBx-NF-κB pathway and contributes to?fibrosis?during human early hepatocellular carcinoma development . Oncotarget, 2017, 8: 27263-27276.
[6] Tibaldi E, Zonta F, Bordin L, et al. The tyrosine phosphatase SHP-1 inhibits proliferation of activated hepatic stellate cells by impairing PDGF receptor signaling . Biochim Biophys Acta, 2014, 1843: 288-298.
[7] Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol, 2013, 3: 1473-1492.
[8] Higashi T, Friedman SL, Hoshida Y. Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev, 2017, 121: 27-42.
[9] Nakamura T, Akiyoshi H, Saito I, et al. Adenovirus-mediated gene expression in the septal cells of cirrhotic rat livers. J Hepatol, 1999, 30: 101-106.
[10] 李扬,周大臣,谢海深,等. 七叶皂苷钠通过抑制 4EBP1 的磷酸化进而减缓CCl₄诱导的大鼠肝纤维化. 中国药理学通报,2020, 36: 577 -582.
[11] Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol, 2017, 14: 397-411.
[12] Ezhilarasan D, Sokal E, Najimi M. Hepatic fibrosis: It is time to go with hepatic stellate cell-specific therapeutic targets . Hepatobiliary Pancreat Dis Int, 2018, 17:192-197.
[13] Aydın MM, Akçalı KC. Liver fibrosis.Turk J Gastroenterol. 2018, 29:14-21.
[14] 陈靖,郑琦,陈薇,等. 大鼠肝纤维化与 microRNA-181a调控肝星状细胞自噬的关系. 中国病理生理杂志,2021, 37: 98-105.
[15] de Oliveira da Silva B, Ramos LF, Moraes KCM. Molecular interplays in hepatic stellate cells: apoptosis, senescence, and phenotype reversion as cellular connections that modulate liver fibrosis. Cell Biol Int, 2017, 41:946-959.

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