Rong Zhong-Hou, Chen Hong-Yuan, Wang Xin-Xing, Wang Zhi-Yi, Xian Guo-Zhe, Ma Bang-Zhen, Qin Cheng-Kun, Zhang Zhen-Hai
Zhong-Hou Rong, Hong-Yuan Chen, Xin-Xing Wang, Zhi-Yi Wang, Guo-Zhe Xian, Bang-Zhen Ma, Cheng-Kun Qin, Zhen-Hai Zhang, Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shangdong University, Jinan 250021, Shandong Province, China.
World J Gastroenterol. 2016 Jun 28;22(24):5540-7. doi: 10.3748/wjg.v22.i24.5540.
To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs.
Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.
The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.
A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.
探讨豚鼠Oddi括约肌(SO)运动功能对胆固醇性胆囊结石形成的机制及影响。
将34只成年雄性Hartley豚鼠随机分为两组,对照组(n = 10)和胆固醇结石组(n = 24),胆固醇结石组再根据处死时间顺序分为4个亚组,每组6只。胆固醇结石组豚鼠给予致胆固醇结石饮食,分别于3、6、9和12周后处死。在每个阶段,用多功能生理记录仪进行SO测压和肌电活动记录。采用定量实时荧光定量PCR(qRT-PCR)检测SO平滑肌中胆囊收缩素A受体(CCKAR)表达水平,采用酶联免疫吸附测定法检测胆固醇结石形成过程中各阶段血清血管活性肠肽(VIP)、胃泌素和胆囊收缩素八肽(CCK-8)水平。
3、6、9和12周组的结石形成率分别为0%、0%、16.7%和83.3%。与对照组相比,9周组肌电活动频率、9和12周组肌电活动幅度以及9周组SO的幅度和频率均显著降低。12周组SO基础压力和胆总管压力显著升高,与对照组相比,6和12周组CCKAR表达水平升高。9和12周组血清VIP显著升高,3和9周组胃泌素显著降低。各组间血清CCK-8无差异。
致胆固醇结石饮食可诱导SO功能障碍。SO张力增加及其活性降低可能在胆固醇结石形成中起重要作用。SO平滑肌中CCKAR表达变化以及血清VIP和CCK-8可能是SO功能障碍的重要原因。