高密度脂蛋白受体SR-BI对细胞内胆固醇外流的影响

胆固醇逆向转运（RCT）是清除内源性胆固醇的重要途径,该过程指高密度脂蛋白（HDL）将多余的胆固醇从外周组织、细胞（包括泡沫细胞）通过载体血浆脂蛋白转运至肝脏,以胆酸的形式排泄或形成类固醇激素等再循环的过程。主要包括细胞胆固醇的流出、酯化及清除,     

高密度脂蛋白对THP-1巨噬细胞B类Ⅰ型清道夫受体的表达及胆固醇流出的影响

目的:观察高密度脂蛋白(HDL)对THP-1巨噬细胞B类I型清道夫受体(SR.BI)的表达及胆固醇流出的影响.方法:用HDL及氧化低密度脂蛋白ox.LDL)处理 THP-1细胞,采用RT-PCR、Western印迹及液体闪烁计数法观察细胞SR-BI的表达及细胞内胆固醇流出的变化.结果:OX-LDL下调THP-1巨噬细胞中sR-BI的袁达,而HDL则上调THP-1巨噬细胞中SR-BI的表达;液体闪烁计数法检测发现OX-LDL减少细胞中胆固醇的流出,HDL可以增加细胞胆固醇的流出,且HDL的效应呈浓度依赖性.结论:HDL可能通过上调THP-1巨噬细胞SR-BⅠ的表达,促进巨噬细胞内胆固醇流出.     

沉淀剂浓度对测定高密度脂蛋白胆固醇的影响

高密度脂蛋白胆固醇在临床上广泛用于冠心病相对危险因素的预测,其测定方法很多,但以沉淀法应用最为广泛。其中磷钨酸镁法由于试剂价廉易得,稳定,且沉淀高甘油三脂血清能力较强,不干扰酶法测定胆固醇,精度符合要求〔1〕,使用更多。在实验中磷钨酸镁的浓度将直接影响沉淀的效果。国内试剂厂家所用沉淀剂浓度相差很大,使用时沉淀剂与血清比例亦不同,这样就使得沉淀剂与血清混合后沉淀剂最终浓度相差更大,磷钨酸镁浓度高者可达500ｍｍｏｌ/Ｌ,而低者仅068ｍｍｏｌ/Ｌ〔2〕。如此悬殊的浓度对结果究竟有何影响,本文就此作了初步探讨,并与直接法…     

游泳对中老年康复者高密度脂蛋白胆固醇的影响

本文总结对31名康复疗养者在海里游泳约4周前后的血脂和脂蛋白与30名不游泳者做的比较试验。游泳组HDL-C值和HDL-C/TC比值显著升高(P<0.05);TC、TG、LDL-C和体重相差下显著。提示康复疗养者游泳锻炼能改善脂蛋白代谢,对动脉粥样硬化有一定意义。     

ABCG1介导的胆固醇外流在SLE患者中的作用及机制研究

目的 探讨ATP结合盒转运蛋白G1(ABCG1)介导的胆固醇外流在系统性红斑狼疮(SLE)患者中的变化及临床意义。方法 选取2017年1月至2021年10月在青岛市市立医院(下称该院)就诊的SLE患者73例作为SLE组,其中合并心血管并发症患者40例,未合并心血管并发症患者33例,另选取同期在该院进行健康体检的52例体检健康者作为健康对照组,通过构建ABCG1高表达质粒载体转染中国仓鼠卵巢细胞(CHO-K1),荧光标记法检测SLE组和健康对照组胆固醇外流情况,计算胆固醇流出率,统计学分析ABCG1介导胆固醇外流的变化。结果 与CHO-K1细胞相比较,在ABCG1表达水平上调的CHO-K1细胞中,健康对照组、SLE组未合并心血管并发症及合并心血管并发症的胆固醇外流率均显著增加,差异有统计学意义(P<0.05);在CHO-K1细胞中,与健康对照组相比较,SLE组胆固醇外流率明显增高,差异有统计学意义(P<0.001),与未合并心血管并发症的SLE组相比较,SLE合并心血管并发症组胆固醇外流率明显增高,差异有统计学意义(P<0.05);在ABCG1高表达的CHO-K1细胞中...     

消除脂蛋白对直接法测定高密度脂蛋白胆固醇影响的方法探讨

目的 研究消除脂蛋白对直接法测定高密度脂蛋白胆固醇影响的方法。方法 用选择性抑制法直接测定。将测定波长放在所用色原的最大吸收峰处,用双波长下去样品空白法和二点法消除干扰。结果 （1）双波长测定的非特异性反应明显小于单波长测定,而双波长下的去样品空白法和二点法测定则进一步缩小了非特异性反应。（2）与推荐方法磷钨酸镁法比较,去样品空白法和二点法的偏差分别为1．73％和2．17％,均小于不去样品空白法的5．6％。（3）乳糜微粒所致的标本混浊和三酰甘油浓度高达11．03mmol/L时,对去样品空白法和二点法测定无影响。（4）低密度脂蛋白（LDL）加入量达5g/L,总胆固醇（TC）和低密度脂蛋白－胆固醇（LDL－C）浓度高达18．7mmol/L和16.59mmol/L时,对去样品空白法无影响：LDL加入量在4.17g/L,TC和LDL－C浓度在15.43mmol/L和13.27mmol/L时,对二点法形成小的负干扰。（5）未去样品空白法在乳糜微粒所致的标本混浊,TG浓度＞4.69mmol/L和LDL加入量从0.88g/L到5g/L时,均受正干扰。结论 双波长下的去样品空白法和二点法能有效消除脂蛋白对直接法测定高密度脂蛋白胆固醇的影响。     

RELMα对动脉粥样硬化清道夫受体表达的影响

目的探讨抵抗素样分子α（RELMα）对与动脉粥样硬化密切相关的巨噬细胞清道夫受体CD36以及平滑肌细胞清道夫受体A（SR-A）表达的影响。方法体外培养巨噬细胞以及平滑肌细胞,用氧化低密度脂蛋白（ox-LDL）I）2及终浓度分别为3 × 10^-6mmol／L,9 × 10^-6mmol/L,2．7 × 10^-5mmol／L的RELMα刺激培养的细胞,24h后收集细胞,用流式细胞仪测定巨噬细胞清道夫受体CD36以及平滑肌细胞SR．A表达。结果OX．LDL明显促进巨噬细胞CD36表达,重组RELMα不影响OX-LDL诱导的体外培养的巨噬细胞清道夫受体CD36的表达,重组RELMα能明显促进OX．LDL诱导的平滑肌细胞SR-A表达（与对照组比较,P〈0．01）。结论RELMa不影响OX．LDL诱导的巨噬细胞清道夫受体CD36的表达,但能促进OX．LDL诱导的平滑肌细胞SR-A表达,提示RELMα可能通过促进SR．A表达从而促进动脉粥样硬化进展。     

消除脂蛋白对直接法测定高密度脂蛋白胆固醇影响的方法探讨

目的研究消除脂蛋白对直接法测定高密度脂蛋白胆固醇影响的方法.方法用选择性抑制法直接测定.将测定波长放在所用色原的最大吸收峰处,用双波长下去样品空白法和二点法消除干扰.[KG2〗结果(1)双波长测定的非特异性反应明显小于单波长测定,而双波长下的去样品空白法和二点法测定则进一步缩小了非特异性反应.(2)与推荐方法磷钨酸镁法比较,去样品空白法和二点法的偏差分别为1.73%和2.17%,均小于不去样品空白法的5.6%.(3)乳糜微粒所致的标本混浊和三酰甘油浓度高达11.03mmol/L时,对去样品空白法和二点法测定无影响.(4)低密度脂蛋白(LDL)加入量达5g/L,总胆固醇(TC)和低密度脂蛋白-胆固醇(LDL-C)浓度高达18.7mmol/L和16.59mmol/L时,对去样品空白法无影响LDL加入量在4.17g/L,TC和LDL-C浓度在15.43mmol/L和13.27mmol/L时,对二点法形成小的负干扰.(5)未去样品空白法在乳糜微粒所致的标本混浊,TG浓度＞4.69mmol/L和LDL加入量从0.88g/L到5g/L时,均受正干扰.结论双波长下的去样品空白法和二点法能有效消除脂蛋白对直接法测定高密度脂蛋白胆固醇的影响.     

烟龄对血清高密度脂蛋白胆固醇水平影响的研究

目的分析烟龄对血清高密度脂蛋白胆固醇(HDL-C)水平的影响。方法对1741例吸烟者的资料,以5年为一个阶段,对7个烟龄组吸烟者的血清HDL-C水平进行分析,并进行组间比较,同时对不同烟龄上下两组之间HDL-C水平的差异进行比较。结果烟龄1～5年组吸烟者血清HDL-C水平为1.34mmol/L,与不吸烟组的HDL-C水平1.43mmol/L相比,差异具有统计学意义(P<0.05)。烟龄6～10年组血清HDL-C水平为1.28mmol/L,与烟龄1～5年组相比,差异无统计学意义(P>0.05)。烟龄6年以上各组之间,以及各不同烟龄上下两组之间HDL-C水平差异均无统计学意义(P>0.05)。结论即使烟龄仅有1年,血清HDL-C水平已显著低于不吸烟者;当烟龄达到5年时,对血清HDL-C水平的影响已与烟龄大于30年者相当。提示吸烟对HDL-C的负面影响在开始建立吸烟习惯早期已能快速且充分地显示出来。建议吸烟者尽早戒除吸烟习惯,不吸烟者不要建立吸烟习惯。     

吸烟对血清高密度脂蛋白胆固醇水平影响的研究

目的探讨吸烟对血清高密度脂蛋白胆固醇(HDL-C)水平的影响程度。方法采用调查问卷与血脂检测相结合的方法,对1741例目前正保持吸烟习惯者与3533例未建立吸烟习惯或已戒烟者的HDL-C水平进行分析;为进一步排除饮酒对HDL-C的影响,还筛选出245例只吸烟不饮酒者,比较不吸烟与吸烟两组HDL-C水平的差异。结果吸烟组的HDL-C水平为1.28mmol/L,不吸烟组的HDL-C水平为1.43mmol/L,两组相比差异具有高度统计学意义(P<0.01);吸烟且不饮酒组的HDL-C水平为1.22mmol/L,与不吸烟组相比差异具有高度统计学意义(P<0.01)。结论吸烟可以导致血清HDL-C水平降低,这或许是吸烟导致冠心病和缺血性脑卒中危险增加的有效机制之一。     

Low‐dose niacin supplementation modulates GPR109A,niacin index and ameliorates Parkinson's disease symptoms without side effects

A 65‐year‐old male, Parkinson's disease patient, was evaluated for GPR109A expression, niacin index, UPDRS scale, handwriting test, and quality of sleep with and without niacin treatment. The evaluation was repeated 3 months after niacin was stopped. Niacin modulated the abovementioned parameters and showed the overall improvement without side effects.     

A possible significant role of zinc and GPR39 zinc sensing receptor in Alzheimer disease and epilepsy

Zinc the essential trace element, plays a significant role in the brain development and in the proper brain functions at every stage of life. Misbalance of zinc (Zn²⁺) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as Alzheimer's disease, Depression, and Epilepsy. In brain, Zn²⁺ has been identified as a ligand, capable of activating and inhibiting the receptors including the NMDA-type glutamate receptors (NMDARs), GABA_A receptors, nicotinic acetylcholine receptors (nAChRs), glycine receptors (glyR) and serotonin receptors (5-HT3). Recently GPR39 has been identified as a zinc-specific receptor, widely expressed in brain tissues including the frontal cortex, amygdala, and hippocampus. GPR39, when binding with Zn²⁺ has shown promising therapeutic potentials. This review presents current knowledge regarding the role of GPR39 zinc sensing receptor in brain, with a focus on Alzheimer’s disease and Epilepsy. Although the results are encouraging, further research is needed to clarify zinc and GPR39 role in the treatment of Alzheimer's disease and Epilepsy.     

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

G‐protein‐coupled receptor 55 (GPR55) has been proposed as an atypical cannabinoid receptor, which is activated by lysophosphatidylinositols and some synthetic or endogenous cannabinoid molecules. The exact role of GPR55 receptors in the central nervous system especially in anxiety needs to be evaluated. In this study, the effects of intracerebroventricular (i.c.v.) administration of agonist and antagonist of GPR55 receptor on anxiety‐related behaviors in rats were investigated. Here, O‐1602 (GPR55 agonist) at the doses of 0.2, 1, and 5 μg/rat increased %OAT and %OAE but not the locomotor activity, showing an anxiolytic response, whereas i.c.v. injection of ML193 (GPR55 antagonist) at the doses of 0.1 and 1 μg/rat increased anxiety‐like behaviors while causing locomotor impairment. The antagonistic effect of ML193 on the anxiolytic‐like effect of O‐1602 was also evaluated. The results showed that ML193 decreased the anxiolytic‐like effect of O‐1602. Based on these results, it may be concluded that central GPR55 may have a role in modulation of anxiety‐like behaviors in rats. Further experiments are needed to elucidate the exact role of these receptors in anxiety.     

Thermofiltration in hypercholesterolemia treatment: analysis of removal and posttreatment cholesterol recovery

Thermofiltration, a system of membrane plasmapheresis for LDL apheresis, is used to treat patients with refractory hyperlipidemia. In this system, the separated plasma is warmed to or above physiologic temperature, filtered with a membrane filter, and returned to the patient on-line. Plasma infusion products are not required. In this study one calculated plasma volume was treated weekly, biweekly, or monthly in patients classified as type II hypercholesterolemic. Reduction and sieving of lipoproteins were evaluated. The reduction ratios of high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were 0.30 +/- 0.06 and 0.58 +/- 0.05, respectively (mean +/- S.D.). Sieving coefficients of the plasma filter for HDLc and LDLc were 0.62 +/- 0.12 and 0.03 +/- 0.02, respectively (mean +/- S.D. of 31 treatments). To evaluate the posttreatment recovery the apparent fractional catabolic rates (FCRa) for total cholesterol and LDLc were calculated. FCRa was 0.151 +/- 0.06 and 0.148 +/- 0.06 day-1 for total cholesterol and LDLc, respectively. The ratio of the posttreatment concentration on the seventh day to the concentration immediately pretreatment was found to be significantly higher for HDLc than for LDLc, 0.92 +/- 0.8 vs. 0.77 +/- 0.1 (mean +/- S.D.), due to faster HDLc recovery. The ratio of LDLc/HDLc was lowered for up to 2 weeks after the treatments.     

Serum amyloid A and high-density lipoprotein cholesterol: serum markers of inflammation in sarcoidosis and other systemic disorders

Hypocholesterolemia has been observed in several inflammatory diseases such as rheumatoid arthritis, myeloproliferative disorders, systemic lupus erythematosus and sarcoidosis. Serum amyloid A is an acute-phase reactant that is related to the high-density lipoprotein cholesterol. This review discusses the relationship between the activation of the cells of the monocyte-macrophage system, determined by the serum amyloid A levels, and the lipid metabolism, measured as alterations in plasma lipoprotein concentrations. The mechanisms of this association during acute inflammation are also discussed in this review.     

ZFN-mediated in vivo gene editing in hepatocytes leads to supraphysiologic α-Gal A activity and effective substrate reduction in Fabry mice

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Effect of obesity and weight reduction on biliary cholesterol saturation and the response to chenodeoxycholic acid

Biliary cholesterol saturation indices (SI's) were measured in fasting duodenal bile from (i) obese and non-obese individuals with and without cholesterol gallstones, (ii) obese individuals undergoing weight reduction and (iii) obese gallstone patients receiving chenodeoxycholic acid (CDCA) therapy. Biliary lipid secretion rates were also measured in three obese subjects before and during 11 days starvation. The mean SI in fifteen non-obese controls (0.89 +/- SEM 0.06) was significantly lower than that in the twenty-four obese without (1.14 +/- 0.07; P less than 0.01), and in the twenty-nine non-obese with gallstones (1.30 +/- 0.05; P less than 0.001) while in sixteen obese gallstone patients, the mean SI of 1.55 +/- 0.06 was significantly higher than that seen in the other three groups (P less than 0.01-0.001). Although fifteen obese subjects lost 15% of their initial body weight during dieting, this did not change their SI's consistently. However in three obese individuals, total starvation did reduce the SI's and significantly lowered the biliary cholesterol secretion rate. Ten obese gallstone patients responded to 15.8 +/- 0.3 mg CDCA kg-1 day-1 by developing unsaturated fasting duodenal bile (SI 0.89 +/- 0.04). A further increase in CDCA dose to 19.0 +/- 0.7 mg kg-1 day-1, as a result of reducing body weight, was more effective in lowering SI's (0.75 +/- 0.06, range 0.51-1.0) than that achieved by increasing the dose to 18.9 +/- 0.46 mg kg-1 day-1 through more capsules per day (SI 0.89 +/- 0.03, range 0.67-1.25). These studies show that (i) biliary cholesterol SI's are greater when obesity and gallstones occur together than in either obesity or gallstones alone, and (ii) although weight loss in obese individuals does not consistently alter biliary cholesterol SI's, it may be beneficial in obese patients receiving CDCA therapy for gallstone dissolution.     

High-density lipoprotein subfractions and influence of endothelial lipase in a healthy Turkish population: A study in a land of low high-density lipoprotein cholesterol

Abstract

Purpose. Low concentration of high-density lipoprotein (HDL) is prevalent in Turkey. Endothelial lipase (EL) regulates lipoprotein metabolism. Small, lipid-poor HDL particles represent more-efficient cholesterol acceptors than their large, lipid-rich counterparts. The aim of this study was to investigate HDL subfractions and the effect of EL on HDL concentrations in healthy Turkish population. Methods. 102 healthy subjects were included in the study (mean age 33.6 ± 10.3 years, 42 female). HDL subfractions were assayed by single precipitation method and EL concentrations were measured by competitive enzyme immunoassay. Results. Mean HDL concentrations were 1.45 ± 0.37 mmol/L in women, 1.10 ± 0.30 mmol/L in men. Small HDL subfraction levels did not differ statistically between < 1 mmol/L and ≥ 1.6 mmol/L total HDL groups. Small HDL was not correlated with EL, low density lipoprotein cholesterol (LDL), triglyceride (TG) and age but positively correlated with total cholesterol and HDL (r = 0.2, p = 0.017; r = 0.2, p = 0.028, respectively). Large HDL was not correlated with age, EL and total cholesterol, and negatively correlated with HDL, LDL, TG (r = ? 0.7, p < 0.001; r = ? 0.2, p = 0.045; r = ? 0.3, p < 0.001, respectively). If subjects were divided into two groups as HDL< 1 mmol/L and HDL > 1.6 mmol/L, mean EL concentrations were 475.83 ± 521.77 nmol/L and 529.71 ± 276.92 nmol/L, respectively (p = 0.086). Conclusion. There were no differences between small HDL concentrations in the HDL low and high groups. Our data did not support EL to be the reason for low HDL in a healthy Turkish population. Our results in a healthy population may serve as a reference for clinical studies on HDL subfractions.     

APOA1/C3/A5 haplotype and risk of hypertriglyceridemia in Taiwanese

BACKGROUND: Apolipoprotein A5 gene (APOA5) has been shown to modulate plasma triglyceride concentrations. We investigated 2 distinct APOA1/C3/A5 haplotypes roles for hypertriglyceridemia. METHODS: We recruited 308 cases of hypertriglyceridemia and 281 normal controls from a hospital. Twelve single nucleotide polymorphisms (SNPs) across the APOA1/C3/A5 gene region were genotyped. RESULTS: One haplotype containing the minor alleles of the APOA5 (-1131T>C, c.553G>T) and APOA1 (-3013C>T,-75G>A) was more prevalent in cases than in controls (11.3% vs. 1.1%, respectively) and was statistically significantly associated with high triglycerides (adjusted odds ratio: 12.83, 95% confidence interval [CI]: 5.1-32.4, P<0.001). Another haplotype that was associated with hypertriglyceridemia (adjusted odds ratio 2.13, 95% CI, 1.37-3.29, P=0.001). Participants carrying both minor alleles of APOA5-1131CC and c.553TT had a 116% higher triglyceride concentration compared with those carrying common allele. CONCLUSIONS: The APOA1/C3/A5 haplotype represents an important locus for predicting risk of hypertriglyceridemia among Taiwanese.     

Excellent response of severe aplastic anemia to treatment of gut inflammation: A case report and review of the literature

BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium.CASE SUMMARY A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However,subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient(namely, psychiatric disorders, hypertension,insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements.CONCLUSION Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.