CAJ | 학술논문

目的探讨通过应用胆碱酯酶抑制剂和胆碱能M受体阻断剂激活α7烟碱型乙酰胆碱受体,观察胆碱能抗炎途径双效活化对阻塞性黄疸大鼠肝损伤和炎症反应的影响.方法成年雄性Wistar大鼠22只,16只手术结扎大鼠胆总管(BDL)做成阻塞性黄疸模型后随机分为治疗组和对照组,每组8只;另设假手术组6只.治疗组每日腹腔注射山莨菪碱(25 mg/kg)和新斯的明(25 μg/kg),对照组给予等量生理盐水,以假手术大鼠作为正常对照组.隔日测量大鼠体重,12 d后处死大鼠,观察肝组织损伤的病理变化,检测肝功能及肝组织和血清中促炎细胞因子的表达水平.结果阻塞性黄疸大鼠体重明显低于假手术组大鼠,治疗组大鼠的体重增长率在治疗3d后与对照组一致.阻塞性黄疸对照组和治疗组转氨酶、胆红素和γ-GT水平均显著高于假手术组(P＜0.05),但两组之间比较差异不显著.治疗组的血清白蛋白水平明显高于对照组.治疗组肝组织病理损害性变化明显轻于对照组.阻塞性黄疸大鼠TNF-α、IL-1β和IL-6的肝组织基因表达水平显著高于假手术组(P＜0.05),但治疗组明显低于对照组(P＜0.05).治疗组和对照组血清TNF-α、IL-1β浓度明显高于假手术组(P＜0.05),但治疗组明显低于对照组(P＜0.05).结论使用胆碱酯酶抑制剂和胆碱能M受体阻断剂双效活化胆碱能抗炎途径,可以明显抑制阻塞性黄疸诱发的促炎基因表达和肝损伤.
목적 탐토통과응용담감지매억제제화담감능M수체조단제격활α7연감형을선담감수체,관찰담감능항염도경쌍효활화대조새성황달대서간손상화염증반응적영향.방법 성년웅성Wistar대서22지,16지수술결찰대서담총관(BDL)주성조새성황달모형후수궤분위치료조화대조조,매조8지;령설가수술조6지.치료조매일복강주사산랑탕감(25 mg/kg)화신사적명(25 μg/kg),대조조급여등량생리염수,이가수술대서작위정상대조조.격일측량대서체중,12 d후처사대서,관찰간조직손상적병리변화,검측간공능급간조직화혈청중촉염세포인자적표체수평.결과 조새성황달대서체중명현저우가수술조대서,치료조대서적체중증장솔재치료3d후여대조조일치.조새성황달대조조화치료조전안매、담홍소화γ-GT수평균현저고우가수술조(P＜0.05),단량조지간비교차이불현저.치료조적혈청백단백수평명현고우대조조.치료조간조직병리손해성변화명현경우대조조.조새성황달대서TNF-α、IL-1β화IL-6적간조직기인표체수평현저고우가수술조(P＜0.05),단치료조명현저우대조조(P＜0.05).치료조화대조조혈청TNF-α、IL-1β농도명현고우가수술조(P＜0.05),단치료조명현저우대조조(P＜0.05).결론 사용담감지매억제제화담감능M수체조단제쌍효활화담감능항염도경,가이명현억제조새성황달유발적촉염기인표체화간손상.
Objective To investigate the influence of double-effect activation of cholinergic antiinflammatory pathway on the liver injury and inflammatory response in obstructive jaundice rats by applying cholinesterase inhibitor and cholinergic M receptor blocker to activate alpha 7 nicotinic acetylcholine receptor.Methods 22 adult male Wistar rats were randomly assigned into three groups:sham operation (SO) group (n=6),bile duct ligation (BDL) induced obstructive jaundice with (BDL treatment group) or without treatment (BDL control group) (n=8 each).The medicine treatment group was given anisodamine (25 mg/kg) and neostigmine (25 μg/kg) daily via intraperitoneal injection after surgery,the control group was given equal amount of normal saline.The body weights of rats in each group were measured every other day.After 12 days,the rats were killed,and the pathological changes of liver injury,liver function and the expression levels of proinflammatory cytokines in the serum and liver tissue were observed.Results The body weight of BDL rats was significantly lower than the SO group rats,and the growth rate of BDL treatment group rats was the same as the rats in BDL control group 3 days after the starting of treatment.The AST,ALT,bilirubin and gamma-GT levels of BDL control and treatment groups were significantly higher than the SO group (P＜0.05),but there was no significant difference between BDL control and treatment groups.The serum albumin level of BDL treatment group was obviously higher than that of BDL control group,but the pathological liver injury was significantly slighter.The gene expression levels of TNF-alpha,IL-1 beta and IL-6 in the liver tissue were significantly higher in BDL groups than SO group (P＜0.05),but BDL treatment group was significantly lower than BDL control group (P＜0.05).In addition the serum TNF-alpha and IL-1 beta concentrations of BDL treatment group and control group were significantly higher than the SO group (P＜0.05),but the BDL treatment group was obviously lower than that BDL control group (P＜0.05).Conclusion The combine application of cholinesterase inhibitor and cholinergic M receptor blocker to activate the cholinergic anti-inflammatory pathway can significantly inhibit the obstructive jaundice induced proinflammatory gene expression and liver injury.