ObjectiveTo summarize the mechanism of endoplasmic reticulum stress (ERS) in liver diseases. MethodWe sorted out and summarized the studies related to ERS and liver diseases in recent years. ResultsEndoplasmic reticulum plays important roles in protein folding, calcium ion storage, and lipid synthesis in cells. ERS will be induced when the number of misfolded/unfolded proteins in the endoplasmic reticulum increases or the calcium ion homeostasis is unbalanced. The endoplasmic reticulum regulates the unfolded protein response through three transmembrane receptor proteins to initiate corresponding pathways for restoring endoplasmic reticulum homeostasis. Prolonged stress can lead to metabolic disorders. Mild ERS can promote the progression of hepatocellular carcinoma, and continuous ERS will induce cell apoptosis and play an anti-tumor effect; ERS can promote lipid accumulation in non-alcoholic fatty liver disease and aggravate the progression of the disease; in hepatic ischemia reperfusion injury, ERS activation will aggravate liver damage. Meanwhile, ERS activation plays an important pathogenic role in the pathogenesis of drug-induced liver injury. ConclusionERS plays a crucial regulatory role in the occurrence and development of liver-related diseases, providing a theoretical basis and new approach for targeted ERS therapy in liver diseases.
ObjectiveTo investigate the diagnostic value of spectral saturation inversion recovery, gradient-echo chemical shift MRI， and proton magnetic resonance spectroscopy in quantifying hepatic fat content. MethodsConventional T1-weighted and T2-weighted scanning (without fat saturation and with fat saturation)， gradient-echo T1W in-phase （IP） and opposedphase （OP） images and 1H-MRS were performed in 31 healthy volunteers and 22 patients who were candidates for liver surgery. Signal intensities of T1WI amp; T1WIFS (SInonfat1, SIfat1), T2WI amp; T2WI-FS (SInonfat2, SIfat2), and IP amp; OP (SIin, SIout) were measured respectively, the relative signal intensity one (RSI1), relative signal intensity two (RSI2)， and fat index (FI) were calculated. Peak values and the area under peak of 1H-MRS were measured, and the relative lipid content of liver cells (RLC ) were calculated. Twenty-two patients accepted liver resection and histological examination after MRI scanning, the proportion of fatty degenerative cells were calculated by image analysis software. Results①Hepatic steatosis group showed higher average values of RSI1, FI， and RLC to non-hepatic steatosis group (Plt;0.05), while there was no significant difference in RSI2 between two groups (Pgt;0.05). ②There was a statistical significant difference in RLC among different histopathological grades of hepatic steatosis, and RLC increased in parallel with histopathological grade (Plt;0.05).There was no significant difference in RSI2, RSI1, and FI among different histopathological grades, although the latter two had a tendency of increasing concomitant with histopathological grade (Pgt;0.05). ③The values of FI and RLC were positively correlated with the PFDC （r=0468, P=0.027； r＝0771， Plt;0.000 1）, while they were not in RSI1 and RSI2 (r=0.411, P=0.057； r=0.191, P=0.392). ConclusionsSPIR, Gradient-echo chemical shift MRI and 1H-MRS can help to differentiate patients with hepatic steatosis from normal persons, the latter also can help to classify hepatic steatosis. In quantifying hepatic fat content, 1H-MRS is superior to gradient-echo chemical shift MRI, while SPIR’s role is limited.
目的 观察罗格列酮钠对血糖控制未达标的2型糖尿病（T2DM）合并与不合并非酒精性脂肪肝（NAFL）患者的降糖疗效和安全性。 方法 2009年1月－2011年1月60例仅用磺脲类和二甲双胍治疗血糖控制未达标的T2DM患者，按合并和不合并NAFL分为观察组和对照组各30例，两组均在原口服降糖药基础上联合加用国产罗格列酮钠4 mg 1次/d，治疗共3个月，观察治疗前后的血糖、胰岛素、糖化血红蛋白（HbA1c）、体质量指数（BMI）、血脂、肝功、血压水平以及药物不良反应，并比较治疗后的血糖达标率。 结果 两组患者治疗后的空腹血糖（FPG）、餐后2 h血糖（2hPG）、HbA1c、空腹胰岛素、甘油三酯和极低密度脂蛋白胆固醇均较治疗前下降，高密度脂蛋白胆固醇较治疗前升高（P＜0.05），而丙氨酸转氨酶、总胆固醇、低密度脂蛋白胆固醇及血压无明显变化（P＞0.05），但观察组治疗后的FPG和2hPG均较对照组下降更明显（P＜0.01），且血糖达标率为73.3%，显著高于对照组的46.7%（P＜0.05），同时观察组餐后2 h胰岛素（2hINS）水平在治疗前后均明显高于对照组而且治疗后有显著下降（P＜0.01），但对照组治疗后2hINS虽然也有下降但无统计学意义（P＞0.05）。观察组治疗前后BMI无明显变化，但对照组治疗后BMI有明显的升高（P＜0.05）。结论 国产罗格列酮钠片对血糖控制未达标的T2DM合并和不合并NAFL患者均有进一步降低血糖、HbA1c以及改善血脂的作用，但对T2DM合并NAFL的患者的降糖疗效更显著，未见加重肝功能损坏，不良反应小，可作为此类患者联合用药的一种选择。
摘要:目的:通过建立高脂血症脂肪肝动物模型,探讨杜仲叶醇提取物(alcohol extractive of Folium Eucommiae,AEFE)对脂肪肝的防治作用。方法:高脂饮食8周加维生素D36×105IU/kg分3d腹腔注射，建立大鼠高脂血症脂肪肝动物模型。各给药组从造模第3周开始分别灌胃给予洛伐他汀(4mg·kg-1·d-1)、 AEFE(70、140和420mg·kg-1·d-1),共给药6周。各组每天灌服等量生理盐水，灌胃容积为0.5mL/100g体重。结果:AEFE用药6周后显示,各剂量组血清胆固醇、甘油三酯和游离脂肪酸、谷丙转氨酶和谷草转氨酶均较模型组明显降低(Plt;005),肝组织丙二醛含量降低和超氧化物歧化酶活性升高,肝脂肪变性和炎症反应减轻,尤以中剂量组作用最明显(Plt;001)。AEFE对肝内肿瘤坏死因子α浓度无明显影响。结论:AEFE改善高脂性大鼠肝脏脂肪变性,此作用可能与其降血脂、抗氧化损伤有关。
目的:探讨青年人群中脂肪肝的相关危险因素。方法:收集2008年在我院体检中心同期体检,年龄≤45岁脂肪肝患者127人,非脂肪肝患者116人,询问病史,进行身高、体重、血生化及B超检查并分脂肪肝组和非脂肪肝组进行比较。结果:脂肪肝组肥胖、饮酒、高血脂、高血糖、肝功异常发病率明显高于对照组。结论:肥胖、饮酒是脂肪肝的重要危险因素,脂肪肝患者多伴有糖脂代谢紊乱及肝功受损。
ObjectiveTo investigate the value of proton magnetic resonance spectroscopy (1H-MRS), gradient dual-echo, and triple-echo sequences in the quantitative evaluation of treatment effect of fatty liver at 3.0T MR.MethodsThirty patients with fatty liver diagnosed by CT or ultrasound who admitted in Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital between August 2017 and May 2018, were enrolled and undergone gradient dual-echo, triple-echo, and 1H-MRS examination before and 3 months after treatment. The fat index (FI) and relative lipid content (RLC) were measured. Fatty liver index (FLI) was calculated from blood biochemical indicators, waist circumference, and BMI at the same time. With the reference standard of FLI, the results before and after treatment measured from MRI were analyzed.ResultsThere were significantly differences of FLI, FIdual, FItriple, and RLC before and after treatment (t=5.281, P<0.001; Z=–3.651, P<0.001; Z=–3.630, P<0.001; Z=–4.762, P<0.001), all indexes decreased after treatment. FIdual and FItriple were positively correlated with FLI before (rs=0.413, P=0.023; rs=0.396, P=0.030) and after treatment (rs=0.395, P=0.031; rs=0.519, P=0.003), the highest correlation factor was FItriple to FLI after treatment. There were no significant correlation between RLC and FLI before and after treatment (P>0.05).ConclusionsIt is feasible to quantitatively evaluate the treatment effect of fatty liver by using 1H-MRS, gradient dual-echo, and triple-echo sequences. Gradient triple-echo sequences has better accuracy, which is technically easy to implement and more suitable for clinical development.
ObjectiveTo investigate the feasibility of proton magnetic resonance spectroscopy (1H-MRS) imaging, by which to quantitatively analyze liver fat content for therapeutic evaluation of fatty liver at 3.0 T MRI. MethodsTwenty-six patients who diagnosed with fatty liver were examined with proton MRS at Siemens Trio Tim 3.0 T MRI before treatment and 3, 6 months after treatment, respectively. The water peak, fat peak, water peak area, and fat peak area were detected, and the relative lipid content 1 (RLC1) and relative lipid content 2 (RLC2)were calculated. Fatty liver index (FLI) was referred to the standard which was calculated from triglycerides (TG), gammaglutamyl-transferase (GGT), waist circumference, and body mass index. ResultsThere were significantly different differences of RLC1 and RLC2 among before treatment and 3, 6 months after treatment (Plt;0.05). Compared with before treatment, the RLC1 and RLC2 values significantly decreased on month 3 or 6 after treatment (Plt;0.05). There were positive correlation between RLC1 or RLC2 and FLI (r=0.476, Plt;0.00; r=0.475, Plt;0.001). The intraclass correlation coefficient was more than 0.75 before treatment, the repeatability was better. ConclusionsProton MRS can quantitatively measure liver fat content. It can be reliably used for dynamic monitoring the therapeutic effects for fatty liver. Proton MRS is accurate, and has a good clinical application in dynamically monitoring the progression of fatty liver and evaluating the therapeutic effects of various treatments.
摘要:目的：探讨成都地区体检人群中丙氨酸氨基转移酶（ALT）升高率与其升高的相关因素,为正确分析引起ALT升高的原因提供相关依据。方法:以参与体检的8734名体检人群为研究对象,收集身高、体重、血压、丙氨酸氨基转移酶、空腹血糖、高密度脂蛋白、低密度脂蛋白、总胆固醇、甘油三酯、血清HBsAg、脂肪肝及胆石症等相关资料进行分析。结果:在全部体检人群中,ALT升高率为1011%,男性ALT升高率为13.70%,女性ALT升高率为6.30%,男性明显高于女性（Plt;0001）；ALT升高组的年龄均数小于ALT正常组（Plt;0001）；在ALT升高的受检者中,脂肪肝、高脂血症、肥胖、糖尿病、胆囊结石、饮酒及乙肝等患病率均高于ALT正常组受检者（Plt;005）。结论:脂肪肝、糖脂代谢紊乱及乙肝是体检人员ALT升高的主要原因；男性和低龄也是体检者ALT升高的危险因素。Abstract: Objective: To investigate the prevalence and relative factors of elevated serum alanine aminotransferase(ALT) levels and providescientific bases for its causes analysis in physical examination people in Chengdu. Methods: Subjects who received medical examination in physical examination center of west China hospital were screened in this study. The information of height, body weight, blood pressure, serum ALT, fasting plasma glucose, highdensity lipoprotein cholesterol, lowdensity lipoprotein cholesterol, total cholesterol, triglyceride, hepatitis B surface antigen (HBsAg) statue, fatty liver and cholelithiasis were collected and analyzed. 〖WT5”HZ〗Results:〖WT5”BZ〗 A total of 8734 cases were included in this study. The total prevalence of elevated ALT was observed in 1011%, including 137% in man and 63% in woman, and this difference between man and woman was statistic significant (P＜0001). The mean age of ALT elevated group was obvious lower than that of normal ALT group (P＜0001). Interesting, the occurrence rates of fatty liver, hyperlipidemia, obesity, diabetes,gallstones, drinking and positive hepatitis B surface antigen in ALT elevated group were all significant higher than that in normal ALT group (P＜005). Conclusion: Fatty liver, glyeolipid metabolism disorder, and hepatitis B were main reasons of elevated ALT. Male and young cases were both high risk of elevated ALT in this study.
Objective To explore the relationship between different diagnostic criteria (ATPIII2002, IDF2005 and CDS2007 criteria) for metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD). Methods A total of 666 elderly males admitted to West China Hospital for routine physical examination were involved in this study in May, 2010. The diagnostic agreement rates of different criteria were compared, along with the relationship between different diagnostic criteria for MS and NALFD. Results The diagnostic agreement of CDS2007 criteria with either IDF2005 or ATPIII2002 criteria was good. However, the agreement of ATPIII2002 with IDF2005 was compromised. The prevalence of NAFLD in MS group was significantly higher than that of non-MS group (Plt;0.01). On the basis of CDS2007 criteria, there was significant correlation between NAFLD and MS (Plt;0.000). Conclusion There is a close relation between NAFLD and all three diagnostic criteria of MS. NAFLD is one of the most important risk factors of MS. The diagnostic agreement of CDS2007 criteria with the other two is good, and there is significant correlation between NAFLD and criteria CDS2007 of MS. CDS2007 is found to be of high accuracy and applicability in the diagnosis of MS in Chinese population including the elderly.
目的：对原发性脂肪肝（PFLD）患者及健康对照的一级亲属中PFLD发生情况、胰岛素抵抗（HOMA-IR）指数以及其他相关代谢指标的测定，了解PFLD是否有家族集聚现象及IR在其发病中的可能作用。方法：PFLD的诊断依据B超为脂肪肝并排除继发性原因。PFLD家系组（A组）共42例，11个家庭。选取与A组年龄、性别构成及生活方式和经济状况相近的健康志愿者家系为对照组（B组）共14例，4个家庭。所有受试者均进行身高、体重、腰围、血压等测定，行糖耐量试验、胰岛素及血脂质等检测，并对受试者的生活方式及文化程度和经济状况行量化打分。结果：A组PFLD 33例（78.57%，A1组），无脂肪肝9例（A2组），说明有家族集聚现象。与B组相比，A1组的体重指数、腰围、舒张压、血总胆固醇和HOMA-IR指数显著高于B组（P＜0.05）；血高密度脂蛋白胆固醇（HDL-C）显著低于B（P＜0.05）；A2组的各项指标与B组相比差异无统计学意义，但变化趋势呈现出腹型肥胖、IR、代谢紊乱和血压偏高；而A1组及A2组与B组的生活方式及经济状况无明显差异。结论：PFLD具有较强的家族聚发现象，其IR程度显著高于对照组；家族中无脂肪肝者存在IR相关的代谢紊乱趋势。说明某种内在或遗传因素如IR可能与PFLD发病有关。