Sphincter of Oddi dysfunction in hypercholesterolemic rabbits.
OBJECTIVE
The mechanisms that trigger gallbladder evacuation dysfunction, the key risk factor for gallstone formation, have not yet been fully elucidated. The sphincter of Oddi (SO) plays important roles in the regulation of gallbladder evacuation and maintenance of normal hydraulic pressure of the biliary tract. The aim of our study was to investigate the effects of hypercholesterolemia on the motility function of SO and the underlying mechanisms of SO dysfunction (SOD).


METHODS
Forty New Zealand white rabbits were divided randomly into the control group fed with standard chow and the experimental (Ch) group fed with a high-cholesterol diet for 8 weeks. Changes in the maximal gallbladder emptying rate, gallbladder evacuation with cholecystokinin-octapeptide (CCK-8) stimulation and SO functions of both groups were measured in vivo; B ultrasound examination was used for dynamic observation of peristaltic movements in vivo; SO pressure was measured using manometry; morphological characteristics were observed by electronic microscope; laser scanning confocal fluorescence microscopy was used to identify changes in [Ca]i and Ca oscillation in primary SO smooth muscle cells (SMCs).


RESULTS
Gallbladder cholestasis was observed during early stages of gallstone formation in Ch rabbits. CCK-8 could not improve the gallbladder cholestatic state in Ch group. Passive dilation of SO significantly improved the cholestatic state in Ch rabbits (P<0.05), although the maximal gallbladder emptying rate was still lower than that of the control group. Manometry data indicted a significant increase in the base pressure of the SO low-pressure ampulla segment and high-pressure segment (P<0.05) in Ch group. laser scanning confocal fluorescence microscopy assay data indicated that [Ca]i in SO cells of Ch group significantly increased and were in a state of overload (P<0.05); Ca oscillation signals in SO cells of Ch group were also abnormal.


CONCLUSIONS
Hypercholesterolemia initially induced SOD, leading to increased gallbladder evacuation resistance and cholestasis. We suggested that [Ca]i overload and/or Ca oscillation abnormality potentially play important roles in the pathogenesis of SOD.
Zhang
Xiao-Yong
XY
Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China. zhang-xy@fmmu.edu.cn
Cui
Guang-Bin
GB
Ma
Ke-Jun
KJ
Wang
Sha
S
Wei
Ya-Ning
YN
Du
Pang
P
Chen
Bao-Ying
BY
Guo
Wei
W
Wang
Xin-Jiang
XJ
Huang
Hai-Dong
HD
Wang
Jian-Hong
JH
Huang
Xiao-Feng
XF
Wang
Chun-Mei
CM
Wang
Yue-Min
YM
Wei
Jing-Guo
JG
D000818:Animals; D001646:Bile / Q000378:metabolism; D020013:Calcium Signaling; D002765:Cholecystography / Q000379:methods; D002779:Cholestasis / Q000209:etiology / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D016473:Gallbladder Emptying; D006937:Hypercholesterolemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D010528:Peristalsis; D011817:Rabbits; D012844:Sincalide; D009803:Sphincter of Oddi / Q000378:metabolism / Q000648:ultrastructure; D046628:Sphincter of Oddi Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D002791:Cholesterol, Dietary; D002784:Cholesterol; D012844:Sincalide