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.
Objective To investigate the relationship between the polymorphism of 7α-hydroxylase (CYP7A1) and cholestero1 cholecystolithiasis. Methods CYP7A-1 genotyping was performed by PCR-RFLP approach in 160 cholesterol cholecystolithiasis patients and 94 control subjects.Results The frequencies of C, A allele of CYP7A1 gene were 83.75%, 16.25% in cholesterol cholecystolithiasis patients and 81.91% and 18.09% in control group. There was no significant difference in frequencies of allele and genotype in A-204C polymorphism between two groups (Pgt;0.05). In control group and cholesterol cholecystolithiasis group， LDL-C levels in AA genotypes were lower than those in CC and CA genotype (Plt;0.05). Conclusion The results indicate that no direct association is found between CYP7A-1 gene and cholesterol cholecystolithiasis，but there is significant correlation between the polymorphism of the CYP7A-1 gene and the levels of LDL-C.
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.
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.
To study of plasma lipoprotein cholesterol and effects of these changes on bile acids and cholesterol in bile during gallstone formation in rabbit model. This gallstone model was induced by high cholesterol diet (HCD). The rabbits were divided into five groups and there were ten animals in each group. The plasma highdensity lipoprotein cholesterol (HDL-C) and its subgroups (HDL2-C, HDL3-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol, triglyceride, phospholipid, bile acids and cholesterol of bile were investigated in different time. The results were as follow: ①As the time of feeding HCD passed by, the plasma total cholesterol, LDL-C and VLDL-C increased markedly (3-week group and 4-week group vs control group, Ｐ＜0.05). Though the plasma HDL-C and its subfractions HDL2-C and HDL3-C did not change significantly, the function of HDL in transporting plasma cholesterol decreased markedly (from 80.00% to merely 3.68%); ②Cholesterol in bile increased gradually and there were significant differences when 3-week group and 4-week group comparing with control group. The concentration of GDCA and GCA in bile changed slightly (Ｐ＞0.05). These results suggest that the changes of plasma lipoprotein cholesterol may affect the metabolism of cholesterol and bile acids and it may take an important role in the formation of gallstone.
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.
Objective In order to study the mechanism of cholesterol gallstone formation through rabbit model which was induced by high cholesterol diet (HCD)Methods the activities of the high density lipoprotein receptor (HDLR) and low density lipoprotein receptor (LDLR) of hepatocytes were investigated. Results The results were as follows: The HDLR activity increased significantly after taking HCD for one week, at the same time, the LDLR activity only increased slightly. Thereafter, the activities of HDLR and LDLR all decreased markedly. As the time of animals taking HCD went on, serum total cholesterol, LDL cholesterol and hepatic cholesterol increased, but bile acids of biliary tract decreased gradually. Conclusion The results suggest that the changes of HDLR and LDLR activities of hepatocytes had no significant effect on bile cholesterol and the decreased HDLR and LDLR activities may cause the reduction some of substrate for bile acids synthesise and play an important role in the formation of gallstone.
【Abstract】Objective To explore the relationship between the expression of MDR1 gene in liver cell and the formation of cholesterol calculus in gallbladder.Methods The mRNA expression level of MDR1 gene in liver cell of the cholesterol calculus group and the normal control group were measured through reverse transcriptionpolymerase chain reaction (RT-PCR)， and microglobulin β2 was used as internal contrast.Results The MDR1 mRNA expression level of the cholesterol calculus group was lower than that of the normal control group(1.30±0.19 vs 2.25±0.28, P＜0.01). Conclusion The formation of cholesterol calculus in gallbladder is related to the reducd expression level of MDR1 gene in liver cell.
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.