Objective To investigate the effects of different particles combination of compound lizards power on the expression of induced nitric oxide synthase (iNOS) protein through regulate and control peroxisome proliferator-activated receptor (PPAR) γ and nuclear transcription factor Kappa B (NF-κB) p65 signaling pathway in the organization of chronic nonspecific ulcerative colitis (CUC) model rats, and reveals its part mechanism on the treatment of CUC.Methods 80 SD rats were randomly divided into blank group, model group, sulfasalazine group, compound lizard power 80 mesh group, 100 mesh group and 80+100 mesh equivalent mixed group, 14 rats in each group.In addition to blank group were treated by 0.85 ml of 0.9% sodium chloride (Nacl) injection instead of enema drugs, the other five groups were treated by mixture enema of 5% 2,4,6-trinitrobenzene sulfonic acid (TNBS) and 50% ethanol with polypropylene tube inserted into colon of 8 cm upper anus.After the models established successfully, the blank group and model group were given 0.9% Nacl injection by gavage in 10 ml/kg, and the sulfasalazine group was given suspensions of sulfasalazine by 0.3 g/kg.Compound lizard power 80 mesh group, compound lizard power 100 mesh group and compound lizard power 80+100 mesh equivalent mixed group were treated by equivalent mixed paste suspension of compound lizard powder of 80 mesh, 100 mesh and 80 + 100 mesh respectively.All rats were anesthetized after 15 days, the lesion site of colon tissue were taken for embedding, and the protein expression in situ of PPAR γ, NF-κB p65 and iNOS were detected by immunohistochemical method in colonic tissue.Results The protein expression of PPARγ, NF-κB p65 and iNOS in intestinal mucosal inflammatory tissue were positive, and there were statistical differences on OD value of positive expression between model group and blank group (P<0.05).There were statistical differences on OD value of positive expression in sulfasalazine group and compound lizard powder groups, compared with model group (P<0.05).There were statistical differences on OD value of positive expression in compound lizard powder groups, compared with sulfasalazine group (P<0.05).There were statistical differences on OD value of positive expression in compound lizard power 80 mesh group, compound lizard power 100 mesh group and compound lizard power 80+100 mesh equivalent mixed group (P<0.05).There were no statistical differences on OD value of positive expression between compound lizard power 80 mesh group and compound lizard power 100 mesh group (P>0.05).The iNOS was positively correlated with the protein expression of NF-κB p65, and NF-κB p65 was negatively correlated with the protein expression of PPAR γ.Conclusion Compound lizard powder and sulfasalazine enteric-coated tablets has exact effects on the treatment of CUC, and the effects in compound lizard power 80+100 mesh equivalent mixed group was best, which suggest that different particles combination of compound lizard powder may have a protective effect for intestinal mucosal injury, its mechanism may be activated the expression of iNOS protein in PPAR γ and NF-κB p65 signal pathways inhibition and regulation by PPAR γ ligand, and thus affect the occurrence and development of CUC inflammation, the PPAR γ, NF-κB p65 and iNOS may be the target on the treatment of CUC.%目的 探讨复方蜥蜴散不同微粒组合剂对慢性非特异性溃疡性结肠炎(CUC)模型大鼠组织中过氧化物酶体增殖物激活受体(PPAR)γ、细胞核转录因子Kappa B(NF-κB)p65信号通路的调控对诱导型一氧化氮合酶(iNOS)蛋白表达的影响,揭示其治疗CUC的部分作用机制.方法 将84只SD大鼠随机分为空白组、模型组、柳氮磺吡啶片组、复方蜥蜴散80目组、复方蜥蜴散100目组、复方蜥蜴散80目+100目等量混合组,每组14只.除空白组灌肠药物用0.9%氯化钠注射液0.85 mL代替,其余5组大鼠均用聚丙烯管插入大鼠肛门上段8 cm结肠内,注入5%2,4,6-三硝基苯磺酸(TNBS)与50%乙醇混合液灌肠.造模成功后,空白组和模型组大鼠予0.9%氯化钠注射液10 mL/kg灌胃,柳氮磺吡啶片组予柳氮磺吡啶悬浊液,浓度按0.3 g/kg.复方蜥蜴散80目组、复方蜥蜴散100目组、复方蜥蜴散80目+100目等量混合组大鼠分别予复方蜥蜴散80目、100目、80目+100目等量混合糊剂混悬液.第15 d后麻醉全部大鼠,取结肠组织病变处包埋,应用免疫组化法检测PPARγ、NF-κBp65、iNOS在结肠组织蛋白的原位表达.结果 PPARγ、NF-KBp65、iNOS蛋白在肠黏膜炎症组织表达均为阳性表达,模型组阳性表达OD值与空白组比较差异有统计学意义(P<0.05);柳氮磺吡啶片组、复方蜥蜴散各治疗组阳性表达OD值与模型组比较差异有统计学意义(P<0.05);复方蜥蜴散各治疗组阳性表达OD值与柳氮磺吡啶片组比较差异有统计学意义(P<0.05);复方蜥蜴散80目组、复方蜥蜴散100目组阳性表达OD值与复方蜥蜴散80目+100目等量混合组比较差异有统计学意义(P<0.05);复方蜥蜴散80目组阳性表达OD值与复方蜥蜴散100目组比较差异无统计学意义(P>0.05).iNOS与NF-κBp65蛋白表达正相关,NF-κBp65与PPARγ蛋白表达负相关.结论 复方蜥蜴散各治疗组、柳氮磺吡啶肠溶片组治疗CUC均有效,其中以复方蜥蜴散80目+100目等量混合组疗效最佳.提示了复方蜥蜴散不同微粒组合剂对肠黏膜损伤可能具有保护修复作用,其机制可能是激活了PPARγ配体抑制调控PPARγ、NF-κBp65信号通路中iNOS蛋白的表达,进而影响CUC炎症的发生发展,PPARγ、NF-κBp65、iNOS可能是治疗CUC的靶位.
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