Objective To study the latest research progress of the formation mechanism of cholesterol stone disease and forming factors of cholesterol stone disease and to provide new theoretical level and develop a new development direction for guiding clinical application. Methods The related literatures at home and abroad were analyzed, compared and summarized, and the current relevant research dynamic of cholesterol stone disease was sketched. Results The formation of cholesterol gallstone is closely related to the abnormal levels of serum lipids metabolism, bacterial and viral infection, and the expression of genes related to cholesterol gallstone. Conclusions The formation of cholesterol calculus disease is a kind of interaction and intricate disease process involving of environmental factors, genetic factors, and biological factors. Although there has been a lot of blood lipid, protein correlation research with cholesterol stone, there are also many studies such as using gene transplantation and gene knockout, but gene technology of cholesterol stone disease diagnosis and treatment is expected to become the new hot research topic.
【Abstract】Objective To observe the bacteria in cholesterol stones by electronic microscope and to explore the role of bacteria in the stone formation.Methods Twelve patients with cholelithiasis underwent operations (male 6, female 6, average age 54.6 years） with cholecystolithiasis 5, extrahepatic and intrahepatic bile duct stone 1, common bile duct stone combining with gallstone 6. The cholesterol stones were observed by electronic microscope.Results There were bacterial structures in the cholesterol stones and cholesterol crystals.Conclusion There are bacteria in the core and peripheral of cholesterol stones, which suggests that bacteria may play an initial role in the formation of cholesterol stones.
Objective To investigate the mRNA expressions of liver X receptor α (LXRα), farnesoid X receptor (FXR), steroid xenobiotic receptor (SXR) and liver receptor homolog 1 (LRH-1) gene in patients with cholesterol gallstone (CGS) disease in order to elucidate the biomolecular pathogenesis of gallstone formation. Methods Twenty-seven patients with CGS (CGS group) and 10 controls without gallstones (control group) were included in this study. Serum lipid composition (total cholesterol, triglyceride, high density lipoprotein cholesterol, apoprotein B, apoprotein A1), gallstone cholesterol concentration and biliary composition (cholesterol, bile salts, lecithin) were assayed. Biliary total lipid and cholesterol saturation index (CSI) were calculated. mRNA expressions of LRH-1, FXR, SXR and LXRα gene were determined by real-time polymorphism chain reaction. Results Serum high density lipoprotein cholesterol concentration was lower in CGS group than that in control group 〔(0.93±0.05) mmol/L vs (1.33±0.09) mmol/L, P＜0.001〕 and serum apoprotein A1 was also lower in CGS group than that in control group 〔(1.19±0.05) g/L vs (1.36±0.06) g/L, P＜0.05〕. There were no differences in serum total cholesterol, triglyceride and apoprotein B between two groups (Pgt;0.05). CSI was higher in CGS group than that in control group (1.17±0.02 vs 0.79±0.10), P＜0.001. Biliary cholesterol was also higher in CGS group than that in control group 〔(7.96±0.39) mol% vs (5.26±0.89) mol%, P＜0.01〕, while biliary total lipid was lower in CGS group than that in control group 〔(104.72±10.51) g/L vs (154.24±14.20) g/L, P＜0.05〕. There were no differences in bile salts and lecithin between two groups (Pgt;0.05). Expression of LRH-1 gene was higher in CGS group than that in control group (14.18±1.80 vs 7.22±2.22), the difference was statistically significant (P＜0.05). There were no differences in mRNA expressions of LXRα, FXR and SXR gene between two groups (Pgt;0.05). Conclusion CGS disease may be related to increased expression of LRH-1 gene.
The aim of the this study was to search for bacterial DNA sequences in cholesterol gallstones with negative bacterial culture by NP-PCR technique. Bacterial gene fragments were amplified in vitro from DNA which were extracted from cholesterol gallstones in gallbladder for identifying the existence of bacteria. The gallbladder gallstones of 30 patients were analysed. Bacterial DNA was found in the stones of 26 patients, indicating that most cholesterol gallstones harbor bacterial DNA.
The hallmark lesions of age-related macular degeneration (AMD) are drusen and basal linear deposit which are lipid substances deposited in Bruch membrane or the compartment on the Bruch membrane. There is a prevailing hypothesis that lipid and its oxidized derivant deposited in retina may have important roles in the pathogenesis of AMD. Lipid oxidation products are toxic, may affect the adjacent cells, induce inflammation, and trigger neovascularization.7-ketocholestoral (7KCh), a naturally occurring oxidized form of cholesterol, had been found to be toxic to retinal cells and able to induce chronic inflammation, which may play a critical role in the development of AMD. However the precise mechanism remains to be elucidated. Thus we will make a brief review of 7KCh and its association with AMD.
Objective To discuss the changes of c-kit/scf mRNA and protein in guinea pig gallbladder fed on high cholesterol diet. Methods Twenty guinea pigs were divided into two equal groups of 10 each：the control group and lithogenic group. Normal diet and high cholesterol diet was given to each group respectively. The period of stone permeation was six weeks. RT-PCR and Western blot were used to determin the expressions of c-kit and scf mRNA and protein. Results RT-PCR results showed that the expressions of c-kit mRNA（t=6.985，P＜0.01） and scf mRNA （t=6.028， P＜0.01）decreased significantly in lithogenic group compared with the control group. Western blot results showed that the expressions of c-kit protein （t=10.256， P＜0.01） and scf protein （t=9.586， P＜0.01）decreased significantly in lithogenic group compared with the control group. Conclusions The expressions of c-kit/scf mRNA and protein decrease during the formation of cholesterol gallstones in guinea pigs fed on high cholesterol diet. Inhibition of c-kit/scf pathway may play a role in the formation of cholesterol gallstones.
ObjectiveTo explore the expressions of transthyretin(TTR) mRNA and its protein in tissues of human gallbladder with cholesterol gallstones, and to explore its role in the formation of cholesterol gallstones. MethodsGallbladder were got from cases of cholesterol gallstones(cholesterol gallstones group, n=25) and cases underwent liver transplantation with normal gallbladder(normal control group, n=9) respectively, who were treated in Ren Ji Hospital and Huashan Hospital. Real time PCR(RT-PCR) and Western blot method were used to determine the expressions of TTR mRNA and its protein respectively. In addition, 2 kinds of artificial model bile system were established to test nucleation time(NT) and nucleation activity, which added TTR and albumin(ALB). ResultsThe expression levels of TTR mRNA and protein in cholesterol gallstones group were 1.51±0.78 and 3.95±0.09 respectively, which were both higher than those of normal control group(P<0.05). The NT were(14.5±1.3)d and(18.0±0.8)d in TTR group and ALB group in small model bile system(P<0.01), which was similar with comprehensive model bile system[(13.5±0.6)d vs. (18.5±1.3)d]. The nucleation activity were 0.81 and 0.73 in small model bile system and comprehensive model bile system respectively. ConclusionsExpression of TTR up-regulates in human gallbladder tissues of patients with cholesterol gallstones, and TTR plays role of nucleation in model bile system, which is related to the formation of cholesterol gallstones.
ObjectiveTo observe the effects of oral Xiaoyan Lidan tablets(XYLDT) on the bile composition(total bile acids, cholesterol, phospholipids) in patients with intrahepatic duct stones after common bile duct exploration(CBDE) with T tube drainage, to explore its possible preventive effects on stone recurrence. MethodsForty consecutive patients with intrahepatic bile duct stones who underwent CBDE with T tube drainage were randomly divided into experi mental group and control group. XYLDT were administrated at day 4 after surgery in experimental group(n=20), while none of medication were given in control group(n=20). 2 mL of bile was collected through T tube in both groups at day 1, 2, 3, 7, 14, and 21 postoperatively. Total bile acids(TBA), cholesterol(CHO), and phospholipids(PLIP) in bile were measured, and TBA/CHO ratio and PLIP/CHO ratio were calculated respectively. The results were statistical analyzed. ResultsThe demographic data in both groups including age, gender, height, weight, preoperative concomitant diseases, operative time, postoperative complications, hospital stays, serum total bilirubin, direct bilirubin, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and amylase were not significantly different(P > 0.05). The measurements of TBA, CHO, PLIP, and the ratio of TBA/CHO and PLIP/CHO in bile were not significant on day 1, 2, and 3 after surgery in both groups(P > 0.05). In experimental group, the TBA, CHO, and PLIP on day 7, 14, and 21 after surgery were significantly increased compared with the control group(P < 0.05). The ratio of TBA/CHO on day 7, 14, and 21 was 2.17±0.29, 2.29±0.44, and 2.59±0.58, the ratio of PLIP/CHO was 2.03±0.68, 2.84±0.64, and 2.86±0.77, respectively, which were also significantly increased compared with the control group(P < 0.05). ConclusionsOral XYLDT can increase the secretion of TBA, CHO, and PLIP, elevate the TBA/CHO and PLIP/CHO ratio, and change the bile composition which may increase the dissolution of cholesterol in the bile. Presumably, oral XYLDT may have preventive effects in the recurrence of intrahepatic bile duct stones.
【Abstract】ObjectiveTo evaluate the relationships between the transporters BSEP， MRP2， MDR3 and cholesterol calculus formation. MethodsTwenty hepatic tissue specimens were taken from consented patients with cholesterol calculus during intraoperative liver biopsy, of which ten were taken from patients without cholesterol calculus. RNA of liver tissue from all the samples was extracted and ultraviolet spectrophotometry was used to measure the content and purity of it. The mRNA and protein expressions of BSEP, MRP2 and MDR3 were determined by reverse transcriptionpolymerase chain reaction (RTPCR) and Western blot analysis, respectively. ResultsRTPCR showed that the mRNA expressions of BSEP, MRP2 and MDR3 in liver were significantly lower in patients with cholesterol calculus （0.47±0.18, 1.12±0.39 and 1.02±0.24） than those in the liver of patients without calculus （0.90±0.42, 2.48±0.89 and 1.94±0.80）,P＜0.01. And Western blot also showed the protein expressions of these transporters were significantly lower in patients with cholesterol calculus （90.16±18.82, 45.43±22.77 and 61.08±14.77） than those in the liver of patients without calculus (186.17±4.34, 160.47±30.19 and 100.84±15.44). ConclusionThe decreased expression of BSEP, MRP2 and MDR3 may correlate with the formation of cholesterol calculus.
ObjectiveTo investigate the association of high density lipoprotein cholesterol (HDL-C) and cholesterol ester transfer protein (CETP) TaqIB mutation with non-arteritic anterior ischemic optic neuropathy (NA-AION) in the Shaanxi Han ethnic population. MethodsThe study cohort consisted of 45 individuals that had been diagnosed with NA-AION and 45 healthy controls (matched for age, gender). None of the cases or controls had a history of diabetes, serious cardio-cerebral vascular diseases, liver and kidney dysfunction that might influence plasma lipid levels. Plasma HDL-C was detected by enzyme-linked immunosorbent one-step, through the Toshiba TBA-40FR automatic biochemical analyzer. CETP TaqIB gene polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques for analysis. B2B2 genotype was only a fluorescence band with 535 bp; B1B1 genotype was 2 fluorescence bands with 361, 174 bp; B1B2 genotype was 3 fluorescence bands with 535, 361, 174 bp. The relative risk of genotype, HDL-C and disease occurrence was analyzed by logistics regression analysis. ResultsThere have no significant difference between NA-AION patients and controls about plasma total cholesterol level and triglyceride level (t=1.907, 1.877; P > 0.05). The plasma HDL-C levels were significantly lower in NA-AION patients than in controls (t=2.367, P=0.022). Compared with controls, the prevalence of B1B1 genotype and B1 allele was higher (χ2=17.289, P=0.001), the prevalence of B2 allele (χ2=15.648, P=0.000) was lower in NA-AION patients. The lower concentration of HDL-C was risk factor of NA-AION (odds ratio=6.143, 95% confidence interval 1.262-29.895, χ2=27.676;P=0.013). The proportion of B1B1 genotype was significantly higher in NA-AION patients than in controls (odds ratio=2.24, 95% confidence interval 2.427-36.323, χ2=10.526; P=0.001). ConclusionsThe low plasma HDL-C is independent risk factor for NA-AION and is associated with the development of NA-AION in the Shaanxi Han ethnic population. CETP TaqIB mutation is associated with low plasma HDL-C in NA-AION in the Shaanxi Han ethnic population.