藤黄酸调节IL-6/STAT3信号通路对急性胰腺炎大鼠肠道损伤的影响OA
Effects of gambogic acid on intestinal injury in rats with acute pancreati-tis by regulating IL-6/STAT3 signaling pathway
目的:探究藤黄酸调节 IL-6/信号转导和转录激活因子 3(STAT3)信号通路对急性胰腺炎(AP)大鼠肠道损伤的影响.方法:72 只 SD 大鼠随机分为假手术(sham)组,AP 组,低、中、高剂量藤黄酸(L、M、H-藤黄酸)组,H-藤黄酸+STAT3 激活剂 colivelin(H-藤黄酸+colivelin)组,每组 12 只.胰胆管注射牛磺胆酸钠建立 AP 模型,sham 组注射生理盐水.造模后,L、M、H-藤黄酸组分别灌胃 25、50、100 mg/kg 藤黄酸,H-藤黄酸+colivelin 组灌胃100 mg/kg 藤黄酸并腹腔注射1 mg/kg colivelin,每日1 次,连续7 d.末次给药后ELISA 法检测血清淀粉酶、脂肪酶及炎性因子(TNF-α、IL-6、IL-18、IL-1β)水平,比色法检测二胺氧化酶(DAO)水平;HE 染色观察胰腺、结肠黏膜组织病理变化;TUNEL、Western blot 法检测结肠黏膜组织细胞凋亡率、紧密连接蛋白-1(ZO-1)及 IL-6/STAT3 信号通路相关蛋白表达.结果:AP 组大鼠胰腺腺泡细胞弥漫性坏死、毛细血管破裂出血、炎性细胞浸润,结肠黏膜上皮脱落、固有层及上皮间隙炎性细胞浸润明显,L、M、H-藤黄酸组大鼠胰腺、结肠黏膜组织上述损伤情况有所减轻;col-ivelin 处理可逆转高剂量藤黄酸对上述损伤的作用.与sham 组比较,AP 组结肠黏膜组织中ZO-1 蛋白表达降低,血清淀粉酶、脂肪酶、DAO、TNF-α、IL-6、IL-18、IL-1β 和结肠黏膜组织细胞凋亡率、IL-6 蛋白表达、p-STAT3/STAT3 升高;与 AP 组比较,L、M、H-藤黄酸组上述指标变化趋势相反,且高剂量效果最好;colivelin 处理可逆转高剂量藤黄酸对除 IL-6 外上述指标的作用(P<0.05).结论:藤黄酸可能通过抑制 IL-6/STAT3 信号通路,改善 AP 大鼠肠道损伤.
Aim:To discuss the effects of gambogic acid on intestinal injury in rats with acute pancreatitis(AP)by regulating the IL-6/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Seventy-two SD rats were randomly divided into sham operation(sham)group,AP group,low-,medium-,and high-dose gambogic acid(L-,M-,H-gambogic acid)groups,and H-gambogic acid+STAT3 activator colivelin(H-gambogic acid+colivelin)group,with 12 rats in each group.The AP model was established by injection of sodium taurocholate into the pancreaticobiliary duct,while the sham group received an equal volume of normal saline.After modeling,the L-,M-,H-gambogic acid groups were administrated with 25,50,and 100 mg/kg gambogic acid by gavage,respectively,and the H-gambogic acid+colivelin group received 100 mg/kg gambogic acid by gavage and intraperitoneal injection of 1 mg/kg colivelin,once daily for 7 consecutive days.After the last administration,serum levels of amylase,lipase,and inflammatory factors(TNF-α,IL-6,IL-18,IL-1β)were detected by ELISA.Serum diamine oxidase(DAO)level was detected by colorimetric method.Pathological changes of pancreatic and colonic mucosal tissues were observed by HE staining.Apoptosis rate of colonic mucosal tissue,expression of zonula occludens-1(ZO-1)and IL-6/STAT3 signaling pathway-related proteins were detected by TUNEL staining and West-ern blot,respectively.Results:The AP group showed diffuse pancreatic acinar necrosis,capillary hemorrhage,inflammatory cell infiltration,colonic mucosal epithelial shedding,and inflammatory cell infiltration in the lamina propria and interepithe-lial spaces.The pancreatic and colonic mucosal damage alleviated in the L-,M-,and H-gambogic acid groups,whereas col-ivelin treatment reversed the effects of high-dose gambogic acid.Compared with the sham group,the AP group showed de-creased ZO-1 protein expression in colonic mucosal tissue,and increased serum levels of amylase,lipase,DAO,TNF-α,IL-6,IL-18,and IL-1β,as well as increased apoptosis rate,IL-6 protein expression,and p-STAT3/STAT3 in colonic mucosal tissue(P<0.05).Compared with the AP group,the L-,M-,and H-gambogic acid groups exhibited opposite trends in the a-bove indicators,and high dose had the best effects(P<0.05).Colivelin treatment reversed the effects of high-dose gambog-ic acid on these indicators except IL-6(P<0.05).Conclusion:Gambogic acid may alleviate intestinal injury in AP rats by inhibiting the IL-6/STAT3 signaling pathway.
陈倩;张莉;刘颖;张丽贤
衡水市人民医院消化内科 河北 衡水 053000衡水市人民医院消化内科 河北 衡水 053000衡水市人民医院乳腺外科 河北 衡水 053000衡水市人民医院消化内科 河北 衡水 053000
医药卫生
藤黄酸IL-6/STAT3信号通路急性胰腺炎肠道损伤大鼠
gambogic acidIL-6/STAT3 signaling pathwayacute pancreatitisintestinal injuryrat
《郑州大学学报（医学版）》 2026 (4)
34-39,6
衡水市市级科技计划自筹项目(2020014046Z)
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