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.
【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.
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.
ObjectiveTo summarize progress of 25-hydroxycholesterol (25-OHC), 27-hydroxycholesterol(27-OHC), and 7α,25-hydroxycholesterol (7α,25-OHC) three oxidized cholesterols in inflammation and immunology and to provide evidence for related basic researches and diseases treatments.MethodThe relevant literatures about these three important oxidized cholesterols in the inflammation and immunology in recent years were reviewed.ResultsThe 25-OHC and 27-OHC could exert the antiviral effects by interfering with various viruses invading the host via various mechanisms. Moreover, the 25-OHC and 27-OHC also played the important regulatory roles in a variety of inflammatory processes and inflammatory diseases. The 7α,25-OHC played the important role in a variety of inflammatory processes by acting on the inflammatory and immune cell membrane receptor G-protein coupled receptor 183 (also known as Epstein-Barr virus-inducible receptor 2).Conclusion25-OHC, 27-OHC and 7α,25-OHC play an important roles in occurrence and development of various inflammatory and immune responses and diseases of inflammatory and immune by acting on a variety of nuclear receptors and membrane receptors.
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.
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.
Objectives To investigate the correlation between blood total cholesterol (TC) and prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and to provide references for clinical treatment and prognosis assessment. Methods We included 232 ISSNHL patients with total deafness in Wenzhou Central Hospital from June 2015 to March 2017 using a prospective cohort design. Recording information including age, gender, hypertension, diabetes mellitus, vertigo, level of blood total cholesterol (TC), level of triglyceride (TG), level of low-density lipoprotein (LDL-C) and LDL/HDL ratio (LDL-C/HDL-C) were collected. Correlation between the prognosis of ISSNHL and blood total cholesterol were analyzed by univariable and multivariable logistic regression analysis. Results The clinical effective rate of patients with TC ranging from 5.2 mmol/L to 6.2 mmol/L was higher than that of patients with TC lower than 5.2 mmol/L (univariable: RR=6.49, 95%CI 3.16 to 13.30, P<0.001; multivariable-adjusted covariates: RR=6.15, 95%CI 2.66 to 14.3,P<0.001) with significant difference. No significant difference was found between patients with TC lower than 5.2 mmol/L and patients with TC higher than 6.2 mmol/L (univariable: RR=1.02, 95%CI 0.52 to 2.00,P=0.960; multivariable-adjusted covariates: RR=1.61, 95%CI 0.55 to 4.73, P=0.386). Gender-specific analysis showed for both male and female groups, the effective rates of patients with TC ranging from 5.2 mmol/L to 6.2 mmol/L were significantly higher than those of patients with TC lower than 5.2 mmol/L. There was no significant difference between patients with TC lower than 5.2 mmol/L and patients with TC higher than 6.2 mmol/L (P>0.05) in either male group or female group. Conclusion The current study suggests that patients with levels of TC ranging from 5.2 mmol/L to 6.2 mmol/L predicts the best prognosis.
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.