【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.
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.
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 review the mechanisms of cholesterol gallstones caused by female hormone so as to explore new treatments to prevent gallstones associated with estrogen and progesterone. Methods The literatures on gallstones related with female hormone were reviewed and the mechanisms of cholesterol gallstones were summarized. Results The cholesterol gallstones mechanisms was affected by estrogen through genomic effects，and the nucleation of cholesterol was promoted by estrogen through nongenomic，which resulted in the formation of cholesterol gallstones. And the bile empty dysfunction associated with estrogen through nongenomic effects was also the reason of cholesterol gallstone formation. The G proteins α subunit responsible for the motility of gallbladder were disrupted by progesterone through genomic effects，and the ionic channels and signal transduction were also interfered through nongenomic pathway，which impaired the contraction of gallbladder. However，the nongenomic effects might not play an important role in the gallstones formation caused by progesterone. Conclusions The mechanisms of cholesterol gallstones formation associated with female hormone are complicated，the understanding of chelesterol gallstones formation mechanisms might be helpful to prevent gallstones associated with estrogen and progesterone.
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 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.
ObjectiveTo investigate the correlation between hyperreflective dots (HRD) and lipid levels and systemic inflammatory factors in patients with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).MethodsA cross-sectional clinical study. From December 2016 to June 2020, 118 eyes of 118 patients with retinal vein occlusion diagnosed in the Department of Ophthalmology, Central Theater Command Hospital of People's Liberation Army were included in the study. Among them, 67 cases of BRVO and 51 cases of CRVO were divided into CRVO group and BRVO group accordingly. Peripheral venous blood was drawn from the patients within 3 days after the eye examination to detect the percentage of neutrophils, monocytes, hypersensitive C-reactive protein (CRP), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a). The ratio of monocytes to high-density lipoprotein (MHR) was also calculated. The 3D OCT-2000 instrument from Topcon (Japan) was used to measure the central retinal thickness (CRT) and the numbers of HRD. According to the different distribution position, HRD is divided into inner retina HRD, outer retina HRD, and total retina HRD.The independent sample t test was used to compare the continuous variables of the two groups, and the χ2 test was used to compare the rates. The correlation between HRD counts and blood lipid levels and peripheral blood inflammation indicators in patients with different types of RVO was analyzed by Spearman correlation analysis.ResultsThe average age of patients in the BRVO group and CRVO group were 60.1±9.5 and 53.6±15.7 years, respectively; the prevalence of hypertension was 53.7% (36/67) and 24.5% (12/51), respectively. Comparison of age (t=2.634) and prevalence of hypertension (χ2=11.298) between the two groups showed statistically significant differences (P＜0.05). Gender (χ2=2.000), course of disease (t=－1.101), prevalence of diabetes (χ2=1.315), eye category (χ2=1.742), baseline visual acuity (t=1.792), intraocular pressure (t=0.708), CRT (t=1.318), and peripheral blood include the percentage of neutrophils, the absolute number of monocytes, CRP, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein(a), MHR (t=－0.559, 1.126, 0.579, 1.299, －0.134, 0.556, 1.230, －0.267, 0.483), the difference was not statistically significant. Correlation analysis showed that the HRD counts in the outer retina of BRVO patients were positively correlated with total cholesterol (r=0.289, P=0.036); the HRD in the inner retina and total HRD counts of CRVO patients were positively correlated with CRP (r=0.406, 0.343; P=0.004, 0.014). There was no correlation between HRD counts and percentage of neutrophils, absolute number of monocytes, triglycerides, high-density lipoprotein, low-density lipoprotein, lipoprotein(a), and MHR (P＞0.05).ConclusionThe number of HRD is related to the blood lipid level in BRVO patients and CRP (an inflammatory index) in CRVO patients.
【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 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.
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.