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目的:探讨Nod样受体家族3(NLRP3)抑制剂CY-09对大鼠急性胰腺炎(AP)的保护机制。方法:60只购自河南实验动物中心的远交群大鼠随机数字表法分为对照组、模型组和治疗组,每组20只。模型组和治疗组大鼠采用2%牛磺酸胆酸钠建立AP模型,对照组不做AP模型。建模后治疗组经腹腔注射CY-09 50 mg/kg;模型组和对照组经腹腔注射等体积生理盐水。治疗24 h后苏木精-伊红(HE)染色观察胰腺组织病理学改变。采用酶联免疫吸附试验(ELISA)分析血清白细胞介素(IL)-1β和IL-18水平,采用自动生化仪检测血清淀粉酶水平;采用蛋白质印迹法(Western blot)分析半胱氨酰天冬氨酸特异性蛋白酶-1前体(pro-Caspase-1)和半胱氨酰天冬氨酸特异性蛋白酶-1(Caspase-1)表达水平。计量数据比较采用方差分析,进一步两两比较采用LSD-n t检验。n 结果:治疗组病理学评分[(6.81±2.01)分]低于模型组[(10.45±3.19)分],差异有统计学意义(n t=3.819,n P<0.05)。治疗组血清淀粉酶水平[(2 091.44±302.81) U/L]低于模型组[(4 912.45±590.32) U/L],差异有统计学意义(n t=4.819,n P<0.05)。治疗组血清IL-1β和IL-18水平[(210.49±19.58)、(310.40±28.71) ng/L]低于模型组血清IL-1β和IL-18水平[(409.34±29.81)、(529.59±38.39) ng/L],差异有统计学意义(n t=6.019、7.012,n P<0.05)。治疗组pro-Caspase-1和Caspase-1表达水平(0.51±0.11、0.32±0.11),模型组pro-Caspase-1和Caspase-1表达水平(0.19±0.09、0.53±0.08),治疗组pro-Caspase-1的表达水平高于模型组,治疗组Caspase-1表达水平低于模型组,差异均有统计学意义(n t=2.193、2.891,n P<0.05)。n 结论:NLRP3抑制剂CY-09可显著抑制NLRP3炎症小体活性,降低pro-Caspase-1激活,降低IL-1β和IL-18水平,进而对急性胰腺炎起到保护作用。“,”Objective:To investigate the protective mechanism of nucleotide binding and oligomerization domain (NOD)-like receptor family, pyrin domain-containing protein 3 (NLRP3) inhibitor CY-09 on acute pancreatitis (AP) in rats.Methods:A total of 60 SD rats from June 2018 to June 2019 were randomly divided into control group, model group and treatment group, n n=20 each. The AP model was established by 2% sodium taurocholate in model group and treatment group, but not in control group. After modeling, the treatment group was intraperitoneally injected with CY-09 (50 mg/kg). Rats in the model group and the control group were intraperitoneally injected with equal volume of normal saline. After 48 h of treatment, hematoxylin and eosin (HE) staining was used to observe the pathological changes of pancreas. The serum levels of interleukin (IL)-1β, IL-18, IL-10 and transforming growth factor-β (TGF-β) were analyzed by enzyme linked immunosorbent assay (ELISA) and the serum amylase level was determined by automatic biochemical analyzer. The expression levels of pro-Caspase-1 and Caspase-1 were detected by Western blotting.n Results:Compared with the model group (10.45±3.19), the pathological score of the treatment group (6.81±2.01) significantly decreased (n t=3.819, n P<0.05). Compared with the model group (4912.45±590.32) U/L, the level of serum amylase in the treatment group (2091.44 ± 302.81) U/L significantly reduced (n t=4.819, n P<0.05). Compared with the levels of serum IL-1 β and IL-18 in the model group [(409.34±29.81), (529.59±38.39) ng/L], the levels of serum IL-1 β and IL-18 in the treatment group [(210.49±19.58), (310.40±28.71) ng/L] significantly decreased (n t=6.019, 7.012, n P<0.05). Compared with the expression levels of pro-caspase-1 and caspase-1 in the model group (0.19±0.09, 0.53±0.08), the expression levels of pro-caspase-1 (0.51±0.11) significantly increased and the expression levels of caspase-1 (0.32 ± 0.11) in the treatment group significantly reduced (n t=2.193, 2.891, n P<0.05) .n Conclusion:NLRP3 inhibitor CY-09 can significantly inhibit the activity of NLRP3 inflammasome, reduce the activation of pro-Caspase-1, and then decrease the levels of IL-1β and IL-18, thus playing a protective role in acute pancreatitis.