胆碱能抗炎通路对胃癌癌前病变炎症反应的调节作用

Regulation of cholinergic anti-inflammatory pathway of inflammation on gastric precancerous lesions

目的探讨胆碱能抗炎通路(CAP)对胃癌癌前病变(PLGC)炎症反应的调节作用。方法将56只Wistar大鼠随机分为正常对照组10只,模型组46只。模型组采用N-甲基-N'-硝基-N-亚硝基胍(MNNG)为主的复合造模法制备PLGC大鼠模型。将造模成功的大鼠随机抽取40只分为模型组、PNU282987低剂量组(1.6 mg/kg)、PNU282987中剂量组(2.0 mg/kg)、PNU282987高剂量组(2.4 mg/kg),每组10只。正常对照组与模型组正常饲养,PNU282987组每日按以上剂量腹腔注射1次,给药3周。检测各组大鼠血清和病变组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)促炎因子的表达。结果 PLGC造模成功的各组大鼠血清及病变组织中TNF-α、IL-6的含量明显高于正常对照组(P<0.05),PNU282987高剂量组(2.4 mg/kg)大鼠血清及病变组织中TNF-α、IL-6的含量低于中、低剂量组及模型组,差异有统计学意义(P<0.05)。结论α7烟碱乙酰胆碱受体(α7nAchRs)激动剂PNU282987可能通过CAP下调TNF-α和IL-6等促炎因子的水平。

Objective To investigate the regulation of cholinergic anti-inflammatory pathway on gastric precancerous lesions and inflammatory reaction.Methods 56 Wistar rats were randomly divided into normal group （n =10）and modeling group （n =46） which were prepared into PLGC rats model by the N-methyl-N＇-nitro-N-nitrosoguanidine （MNNG） based composite modeling.Then 40 rats selected from the successfully modeling rats were randomly divided into model group,PNU282987 low dose group （1.6 mg/kg）,PNU282987 dose group （2.0 mg/kg）,PNU282987 high doses group （2.4 mg/kg）,（n =10）.The control group and model group were fed normally.PNU282987 groups were given above daily doses of PNU282987 by intraperitoneal injection for three weeks.Then the expressions of TNF-α,IL-6 in serum and stomach tissue were detected.Results The contents of TNF-o,IL-6 in serum and stomach tissue of PLGC groups were significantly higher than those of control group （P ＜ 0.05）.The contents of TNF-α,IL-6 in serum and stomach tissue of PNU282987 high dose group （2.4 mg/kg） were lower than the low-dose group,dose group and model group （P ＜ 0.05）.The difference was significant.Conclusion The α7nAchR agonist PNU282987 can down-regulate the level of TNF-α and IL-6 through the cholinergic anti-inflammatory pathway.