胆囊收缩素对胆固醇结石豚鼠离体胆囊肌条的影响

Effects of cholecystokinin on gallbladder muscle stripes of guinea pigs with cholesterol gallstone in vitro

目的:建立胆固醇结石实验动物模型,探讨胆囊收缩素(cholecystokinin,CCK)对胆固醇结石豚鼠离体胆囊肌条收缩的影响,并研究胆道动力因素在胆固醇结石形成中的作用.方法:喂养致石饲料构建豚鼠胆固醇结石模型.采用灌流法加药,利用张力换能器记录豚鼠离体胆囊肌条张力的变化,观察10-9、10-8、10-7mol/L的CCK-8对正常豚鼠离体胆囊肌条(A组)、喂养致石饲料4wk(B组)、8wk(C组)豚鼠离体胆囊肌条及正常豚鼠损伤Cajal间质细胞(interstitial cell of cajal,ICC)后离体胆囊肌条(D组)的影响.结果:A组无结石发生,B组及C组共有13例结石发生;A组、B组及C组加入CCK后收缩振幅均增加,呈浓度依赖性;B、C两组振幅加入CCK后的效应值同A组相比变小,起作用时间慢(P<0.05);损伤胆囊ICC后,收缩幅度增加不明显,与CCK浓度无显著差异,而与A组相比效应值有显著性差异(10-9mol/L:0.461±0.071vs1.461±0.252;10-8mol/L:0.608±0.118vs2.484±0.283;10-7mol/L:0.641±0.129vs3.312±0.311,均P<0.01).结论:离体胆囊肌条肌张力降低及对CCK的效应性降低在胆囊结石病的发生发展中有重要作用;而损伤ICC后,胆囊离体肌条对CCK的效应性明显降低,ICC可能在胆囊结石等胆囊动力性疾病中发生作用.

AIM： To establish an animal model of cholesterol stone and to explore the effects of cholecystokinin （CCK） on gallbladder muscle stripes of guinea pigs with cholesterol stone in vitro as well as to investigate the role of biliary kinetics in cholesterol stone formation. METHOOS： The animal model of cholesterol stone was established by feeding guinea pig with stone-leading forage. The guinea pigs were assigned to four groups： group A （the normal guinea pigs）, group B （stone-leading forage for 4 wk）, group C （stone-leading forage for 8 wk）, and group D （the normal guinea pigs with injury of interstitial cell of cajal （ICC）. Effects of 10^-9, 10^-8 and 10.7 mol/L cholecystokinin （CCK） on gallbladder muscle stripes of guinea pigs in vitro among the four groups were recorded and analyzed. RESULTS： No cholesterol stone was observed in group A, and a total of 13 cases of cholesterol stone were observed in group B and C. The am- plitude of contraction showed a dose-indepen- dent relationship with CCK-8 in groups A, B and C. Compared with group A, there was statistically significant diffference in group B and group C （P 〈 0.05）. The contraction of smooth muscle was nearly abolished when interstitial cells of Cajal were destroyed using methylene blue incubation and intensive illumination. Although CCK was administered, there was no significant difference in the amplitude of the contraction of smooth muscle strip in group D （10^-9 mol/L： 0.461 ± 0.071 vs 1.461 ± 0.252; 104 mol/L： 0.608 ± 0.118 vs 2.484 ± 0.283; 10^-7 mol/L： 0.641 ± 0.129 vs 3.312 ± 0.311, all P 〈 0.01）. CONCLUSION： Muscular tension is significantly inhibited following injury of interstitial cells of Cajal. The damage of interstitial cells of Cajal may be an important factor related to cholelithiasis.