To Investigate The Mecdhnisms Of Gallbladder Hypomotility In The Patients With Gallstone And Diabetes Mellitus

Objective: To investigate the mechanisms of gallbladder hypomotility result from the alteration of gallbladder wall by pathological and molecular biological methods in patients with gallstone and diabetes mellitus.Methods: Twenty patients admitted in the department of hepatobiliary surgery, the Second Affiliated Hospital of Chongqing University of Medical Science from March 2003 to October 2003 were included in our study.Patients were devided into two groups.Ten patients with both gallstone and diabetes mellitus belong to group A and ten patients with simple gallstone belong to group B. (1)All the patients' gallbladder emptying function were measured with B ultrasound before operation.(2) Open cholecystectomy were performed under general anesthesia, gallbladder tissues were obtained during the operation .The arterioles of gallbladder were rinsed with PAS reagent and analyzed with BEIHANG CM-2000B biological and medical photo system.(3)Ultrastructural alterations of gallbladder arterioles were detected with transmission electronic microscopy in group A and B respectively.(4)RT-PCR was used to explore gene expression of CCK-A receptor of gallbladder wall in all the patients. Results: (1) In group A, gallbladder volumes of fasting(V0) and two hours later after fatty food(V2) increased (32.06±5.05 vs 23.35±2.70,19.57±3.91 vs 10.30±1.65).The difference has statistical significance(p<0.001). The ejective rate of gallbladder two hours later after eating GBEF2(%)decreased (39.77±6.46 vs 55.19±10.35,P=0.001). (2) In group A, the area ratio of arterioles wall to whole arterioles in cross section(0.81±0.09) was significantly higher than that of group B(0.58±0.15)(p<0.01).Their average optical density was also higher than that of the latter(0.41±0.07 vs 0.30±0.12,p<0.01).The size of arterioles(diameter) had no significant relation to the area ratio(p>0.05).(3) The electron microscope detected ultrastructral alterations:In group A, mitochondrions in the smooth muscle cell were swelling, vacuoled and part of crista were extincted.The myofilaments were rarefaction and disorderly arrayed and part of which were lysis and discontinuous. In group B, mitochondria in the smooth muscle cell were regularly arrayed and small.Uder the nuclear membrane heterochromatin clustered was visible.(4) RT-PCR reveals that group A had lower mRNA expression of CCK-A receptor than that of group B (0.400±0.068 vs 0.622±0.070,P﹤0.01).Conclusions: The emptying function was significantly impaired in patients with gallstone and diabetes mellitus.The mechanisms were as follows: The wall of arterioles' thicker and stenosis of arterioles lead to the worse blood supplyment of gallbladder.(2) Swelling of mitochondrions, rarefaction and derangement of myofilaments in smooth muscle cell may contribute to abnormal gallbladder contractility.(3) The down-regulation of gene expression of CCK-A receptor plays an important role in gallbladder hypomotility.Cholesterol crystal formation as a result of increased gallbladder volume and decreased ejection fraction in diabetic patients which may result from hypotonicity and stasis and thus this was probably basis of the higher incidence of gallstones.