基于TLR4/NLRP3通路探讨消炎散对急性胰腺炎的影响及作用机制OA
Xiaoyansan alleviates inflammatory damage in acute pancreatitis via inhibiting the activation of the TLR4/NLRP3 pathway
目的 探究消炎散对急性胰腺炎(AP)小鼠的干预作用及其作用机制.方法 将40只 雄性 C57BL/6J 小鼠随机分为对照组、AP 组、低剂量消炎散组、中剂量消炎散组、高剂量消炎散组,每组8 只.除对照组外,其余各组小鼠均通过腹腔注射雨蛙肽建立 AP 模型,低、中、高剂量消炎散组在造模后分别予以1,2,4 g/kg 消炎散灌胃,均1 次/d,连续灌胃7 d.测定小鼠腹水量,全自动生化分析仪检测血清淀粉酶(AMY)和脂肪酶(LPS)水平,ELISA 法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-18(IL-18)水平,HE 染色观察胰腺组织病理形态,免疫组化染色检测胰腺组织中 Toll 样受体4(TLR4)和 NOD 样受体热蛋白结构域相关蛋白3(NLRP3)阳性表达情况,Western blot 法检测胰腺组织中 TLR4、髓样分化因子88(MyD88)、磷酸化核因子-κB(p-NF-κB)、核因子-κB(NF-κB)、NLRP3、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)表达情况.结果 与对照组比较,AP 组小鼠腹水量及血清 AMY、LPS、TNF-α、IL-6、IL-18 水平均明显升高(P 均<0.05);胰腺组织结构破坏、间质增宽、腺泡细胞变性以及大量炎症细胞浸润;胰腺组织中 TLR4、NLRP3 阳性表达平均光密度值及TLR4、MyD88、p-NF-κB、NLRP3、Caspase-1蛋白相对表达量均明显升高(P 均<0.05).与 AP 组比较,消炎散各组小鼠腹水量及血清 AMY、LPS、TNF-α、IL-6、IL-18 水平均明显降低(P 均<0.05);胰腺组织病理损伤及炎症细胞浸润减轻;胰腺组织中 TLR4、NLRP3 阳性表达平均光密度值及 TLR4、NLRP3、Caspase-1 蛋白相对表达量均明显降低(P 均<0.05),且中剂量消炎散组和高剂量消炎散组 MyD88、p-NF-κB 蛋白相对表达量也均明显降低(P 均<0.05).结论 消炎散可能通过抑制 TLR4/NLRP3 通路的激活而减轻AP 炎性损伤.
Objective It is to explore the therapeutic effect of Xiaoyansan on mice with acute pancreatitis(AP),and to explore its mechanism of action.Methods Forty male C57BL/6J mice were randomly divided into control group,AP group,low-dose,medium-dose and high-dose groups of Xiaoyansan,with 8 mice in each group.The mice of all groups except for the control group were intraperitoneally injected with caerulein to establish AP models.After modeling,the low-dose,medi-um-dose and high-dose groups of Xiaoyansan were given Xiaoyansan 1,2,4 g/kg via gavage,respectively,all once daily,continuously treated for 7 days.The ascites volume of mice in each group was measured,and the levels of amylase(AMY)and lipase(LPS)in serum of mice in each group were measured by automatic biochemical analyzer,the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-18(IL-18)in serum were measured by ELISA,the pathological changes of pancreatic tissues of mice in each group were observed by HE staining,the positive expressions of Toll-like receptor 4(TLR4)and NLR family pyrin domain protein 3(NLRP3)in pancreatic tissues of mice in each group were detected by immunohistochemical staining,the expressions of TLR4/NLRP3 pathway-related proteins TLR4,myeloid differentiation factor 88(MyD88),phosphorylated nuclear factor-κB(p-NF-κB),nuclear factor-κB(NF-κB),NLRP3,and cysteine protease-1(Caspase-1)in pancreatic tissues of mice in each group were detected by Western blot.Results Compared with the control group,the ascites volume and the levels of AMY,LPS,TNF-α,IL-6 and IL-18 in serum of mice in the AP group were significantly increased(all P<0.05);the pancreatic tissue structure was destroyed with wid-ened interstitial tissue,degenerated acinar cells and infiltration of a large number of inflammatory cells;the mean optical density values of expressions of TLR4 and NLRP3 in pancreatic tissue,as well as the relative protein expressions of TLR4,MyD88,p-NF-κB,NLRP3 and Caspase-1 were all significantly increased(all P<0.05).Compared with the AP group,the ascites volume and the levels of AMY,LPS,TNF-α,IL-6 and IL-18 in serum of mice in each dose groups of Xiaoyan-san were significantly decreased(all P<0.05);the pathological lesions and inflammatory cell infiltration in pancreatic tis-sue were alleviated;the mean optical density values of expressions of TLR4 and NLRP3 in pancreatic tissue,as well as the relative protein expressions of TLR4,NLRP3 and Caspase-1 were all significantly decreased(all P<0.05),furthermore,the relative protein expressions of MyD88 and p-NF-κB were also significantly increased in the medium-dose and high-dose groups of Xiaoyansan.Conclusion Xiaoyansan can inflammatory damage in acute pancreatitis via inhibiting the activation of the TLR4/NLRP3 pathway.
焦敏;袁贺霞;康莹莹;阎新燕;于鲁海;李红健;吴建华
新疆维吾尔自治区人民医院,新疆 乌鲁木齐 830001新疆维吾尔自治区人民医院,新疆 乌鲁木齐 830001||新疆维吾尔自治区临床药学研究所,新疆 乌鲁木齐 830001新疆维吾尔自治区人民医院,新疆 乌鲁木齐 830001||新疆维吾尔自治区临床药学研究所,新疆 乌鲁木齐 830001新疆维吾尔自治区人民医院,新疆 乌鲁木齐 830001||新疆维吾尔自治区临床药学研究所,新疆 乌鲁木齐 830001新疆维吾尔自治区人民医院,新疆 乌鲁木齐 830001||新疆维吾尔自治区临床药学研究所,新疆 乌鲁木齐 830001新疆维吾尔自治区人民医院,新疆 乌鲁木齐 830001||新疆维吾尔自治区临床药学研究所,新疆 乌鲁木齐 830001新疆维吾尔自治区临床药学研究所,新疆 乌鲁木齐 830001
医药卫生
急性胰腺炎消炎散Toll样受体4NOD样受体热蛋白结构域相关蛋白3炎症
acute pancreatitisXiaoyansanToll-like receptor 4NLR family pyrin domain-containing protein 3in-flammation
《现代中西医结合杂志》 2026 (12)
1637-1643,7
新疆维吾尔自治区卫生健康青年医学科技人才专项科研项目(WJWY-202458)
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