Capsaicin对NAFLD小鼠 肝脏脂肪变性、炎症与坏死的改善作用研究

目的研究辣椒素(Capsaicin)对非酒精性脂肪性肝病(NAFLD)小鼠肝脏脂肪变性、炎症与坏死的改善作用。方法取24只C57/B6小鼠,通过高脂饮食诱导建立NAFLD小鼠模型,随机分为对照组(给予常规饲料喂养)、模型组(给予高脂饮食诱导NAFLD动物模型)、实验组(给予高脂饮食诱导NAFLD动物模型+capsaicin干预),三组各8只。对三组小鼠肝脏行苏木精-伊红染色,观察小鼠肝脏病理形态学变化;比较三组小鼠血糖水平、血脂四项和肝功能指标的差异。结果相比对照组,模型组小鼠肝脏可见脂肪体积增大,明显脂肪变性,核被挤向一侧,气球样变性和坏死,并且肝小叶中心出现大量炎性细胞浸润和明显坏死。相比模型组,实验组小鼠肝脏脂肪细胞排列相对完整,脂肪体积明显缩小,脂肪变性、炎症程度和坏死明显减轻。相比对照组,模型组小鼠血清空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白-胆固醇(LDL-C)含量明显增高,高密度脂蛋白-胆固醇(HDL-C)显著下降(P 0. 05);相比模型组,实验组小鼠血清FBG、TC、TG及LDL-C含量显著降低,HDL-C含量明显升高(P 0. 05)。相比对照组,模型组小鼠天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)及谷胱甘肽转移酶(GST)活性明显升高(P0. 05);相比模型组,实验组小鼠AST、ALT及GST活性明显下降(P 0. 05)。经苏木精-伊红染色可知,实验组小鼠肝脏脂肪变性、炎症程度和坏死明显减轻。结论 Capsaicin可有效改善高脂饮食诱导NAFLD小鼠肝脏脂肪变性、炎症与坏死,具有保护小鼠肝脏功能的作用。     

剪切波弹性成像诊断大鼠非酒精性脂肪肝病的实验研究

目的 探讨剪切波弹性成像技术(SWE)在诊断大鼠非酒精性脂肪肝(NAFLD)的价值。方法 将52只雄性SD大鼠随机分为对照组12只和实验组40只,实验组分别喂养蛋氨酸和胆碱缺乏饲料1w、2w、3w和4w(各10只)构建不同程度的NAFLD模型,造模完成后麻醉及处死状态进行剪切波弹性成像(SWE)测量肝脏硬度(LSMa、LSMb),计算测量结果标准差(SD),解剖肝脏SWE检测离体肝脏硬度(LSMc),切除部分肝脏行病理学检查。应用受试者工作特征曲线(ROC)下面积(AUC)评估不同状态下SWE诊断NAFLD的效能。结果 病理检测大鼠正常组17只,脂肪变性组35只。正常组与脂肪变性组麻醉状态肝脏硬度检测结果标准差(SD)为[(1.70±0.56)kPa、(1.86±1.21)kPa],显著高于处死SD[(0.92±0.65) kPa、(1.08±0.73)kPa,P＜0.05],均显著高于离体SD[(0.26±0.16) kPa、(0.33±0.16)kPa,P＜0.05]；脂肪变性组LSMb为(3.95±1.78)kPa,显著高于正常组[(2.91±1.53)kPa,P＜0.05],脂肪变性组LSMc为(1.53±0.32)kPa,显著高于正常组[(1.23±0.16)kPa,P＜0.05],脂肪变性组LSMa与正常组无显著差异(P＞0.05)；LSMb、LSMc诊断肝脂肪变性AUC分别为0.69、0.86,敏感性特异性分别为60.0%、60.0%和82.4%、100%。结论 NAFLD大鼠LSM显著高于正常组,优化仪器性能及测量方法后,SWE在诊断大鼠NAFLD将具有良好的效能,值得进一步研究。     

有氧运动对非酒精性脂肪性肝病大鼠肝脏脂质沉积的影响及作用机制探讨

目的 观察有氧运动对非酒精性脂肪性肝病（NAFLD）大鼠肝脏脂质沉积及单酰甘油O-酰基转移酶1（MGAT1）信号通路的影响,为NAFLD患者康复干预提供参照依据。 方法 选取雄性SD大鼠喂饲含45%脂肪的高脂饲料6周。待证实大鼠已诱发NAFLD后,采用随机数字表法将其分为运动组、安静组及饮食调整组,运动组及安静组大鼠均继续给予高脂饮食,运动组同时辅以8周有氧运动,饮食调整组则恢复正常饮食并保持安静状态。于干预8周后利用HE染色法检测各组大鼠肝组织脂质蓄积并计算肝脏脂肪变性指数,采用Western blot法检测大鼠肝脏MGAT1及过氧化物酶体增殖物激活受体γ（PPARγ）蛋白表达水平。 结果 经8周干预后与安静组比较,发现运动组和饮食调整组大鼠肝脏脂肪变性指数［（分别为（31.5±4.7）%和（25.1±3.9）%］均明显下降（P<0.05）,运动组肝脏MGAT1蛋白表达量（0.46±0.15）明显降低（P<0.05）,PPARγ蛋白表达量（2.16±0.37）明显升高（P<0.05）,饮食调整组肝脏MGAT1蛋白表达量（0.89±0.26）无显著变化（P>0.05）,PPARγ蛋白表达量（1.78±0.35）明显升高（P<0.05）;与饮食调整组比较,运动组大鼠肝脏脂肪变性指数明显升高（P<0.05）,肝脏MGAT1蛋白表达量明显降低（P<0.05）,PPARγ蛋白表达量无显著变化（P>0.05）。 结论 有氧运动可显著改善NAFLD大鼠肝脏脂质沉积,其作用机制可能与抑制MGAT1信号通路有关;有氧运动可能是NAFLD患者康复干预的重要手段。     

白藜芦醇对高脂饮食诱导肾损伤小鼠肾组织单核细胞趋化蛋白1及转化生长因子β1表达的影响

目的观察白藜芦醇(resveratrol,Res)对高脂饮食诱导肾损伤小鼠肾组织单核细胞趋化蛋白1(monocyte chemotactic protein-1,MCP-1)及转化生长因子β1(transforming growth factor-β1,TGF-β1)表达的影响,并探讨其肾脏保护机制。方法 24只健康雄性C57BL/6小鼠随机分为3组,每组7只:正常对照(normal control,NC)组、高脂饮食(high-fat diet,HFD)组和高脂饮食+白藜芦醇干预(high-fat diet with resveratrol intervention,HFD+Res)组。HFD+Res组小鼠每日予以白藜芦醇[35 mg/(kg·d)]灌胃,NC和HFD组予以同等剂量的羧甲基纤维素钠灌胃。12周时,常规生化检测血清总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、血清肌酐(serum creatinine,Scr)及尿素氮(blood urea nitrogen,BUN)水平,采用HE染色法观察肾组织病理学改变,免疫组织化学法、蛋白印迹法检测肾组织中MCP-1和TGF-β1的表达水平。结果正常对照组、高脂饮食组和高脂饮食+白藜芦醇干预组3组间在TC(F=48.688,P0.001),TG(F=15.361,P=0.001),LDL(F=50.401,P0.001),Scr(F=27.143,P0.001)及BUN(F=23.369,P0.001)的差异具有统计学意义。与NC组及HFD+Res组相比,HFD组小鼠的TC、TG、LDL、Scr、BUN水平显著增高(与NC组比较:P0.001;P=0.002;P0.001;P0.001;P0.001;与HFD+Res组比较:P=0.022;P=0.027;P0.001;P=0.001;P=0.001)。HE染色显示,HFD组肾小球系膜细胞和基质稍增多,肾小管上皮细胞胞质增多,HFD+Res组病理损伤减轻。免疫组化结果显示,HFD组MCP-1及TGF-β1表达高于NC组(P=0.004;P0.001)及HFD+Res组(P=0.023;P=0.007),蛋白印迹结果同样显示:HFD组MCP-1及TGF-β1表达高于NC组(P=0.013;P=0.002)及HFD+Res组(P=0.044;P=0.039)。结论 MCP-1和TGF-β1可能参与了高脂肾损伤发病及进展,白藜芦醇可能通过下调其表达起到肾脏保护作用。     

黄连素对高脂饮食诱导非酒精性脂肪性肝病小鼠肝脂毒性的保护作用及相关机制研究

目的研究黄连素对高脂饮食诱导非酒精性脂肪性肝病(NAFLD)小鼠肝脂毒性的保护作用及其可能作用机制。方法将24只C57BL/6J雄性小鼠随机分为对照组(给予基础饲料进行常规饲养)、高脂组(给予高脂饮食)及干预组(在高脂饮食的同时应用黄连素200 mg/kg进行灌胃3个月),三组各8只。对小鼠原代肝巨噬细胞进行培养,分为A组(未进行处理)、B组(应用0. 5 mmol/L棕榈酸)、C组(应用黄连素1μmol/L)、D组(应用0. 5 mmol/L棕榈酸+黄连素1μmol/L)。检测小鼠空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、天门冬氨酸氨基转移酶(AST)及丙氨酸氨基转移酶(ALT)浓度;用油红染色法观察三组小鼠肝脏脂质的沉积状况;检测小鼠肝组织白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)、血清脂多糖水平及促炎细胞因子表达水平。结果高脂组血清FBG、TC、TG、AST及ALT浓度显著高于对照组(P 0. 05);干预组血清FBG、TC、TG及ALT浓度较高脂组显著下降(P 0. 05)。高脂组小鼠肝组织中IL-6和血清脂多糖水平显著高于对照组,干预组小鼠肝组织中IL-6和血清脂多糖水平显著低于高脂组(P 0. 05)。经透射电镜观察可见,B组原代肝巨噬细胞脂质沉积明显,可见胞质中诸多不规则形脂滴; C组与A组原代肝巨噬细胞形态和结构并无显著差异; D组原代肝巨噬细胞内脂滴较少。高脂组小鼠原代肝巨噬细胞中IL-6和TNF-α表达水平显著高于对照组(P 0. 05);干预组小鼠IL-6和TNF-α表达水平较高脂组显著下降(P 0. 05)。结论高脂饮食诱导的NAFLD小鼠应用黄连素进行干预可有效改善其肝脏脂质沉积,减轻肝脏炎症损伤程度,且作用可能与抑制脂多糖生成,进一步阻滞肝内巨噬细胞中炎症因子IL-6和TNF-α等的释放密切相关。     

利拉鲁肽对NAFLD大鼠的保护作用及其与ERp46蛋白表达的相关性研究

目的研究利拉鲁肽对非酒精性脂肪性肝病(NAFLD)大鼠的保护作用及其与ERp46蛋白表达的相关性。方法取24只雄性SD大鼠随机分为对照组(8只,正常饲养)和实验组(16只,高脂饮食);喂养3个月后,将实验组随机分为A组(给予生理盐水)和B组(给予利拉鲁肽100 g/kg)各8只。各组均行苏木精-伊红(HE)染色处理,并进行正常葡萄糖-高胰岛素钳夹试验,采用TUNEL法检测肝细胞凋亡情况;采用Western印迹法对各组大鼠肝脏组织中ERp46蛋白的表达情况进行检测。结果 A组葡萄糖输注率较对照组明显下降(P 0. 05); B组大鼠葡萄糖输注率较A组显著升高,但较对照组明显下降(P 0. 05)。A组肝细胞凋亡率较对照组明显升高(P 0. 05); B组大鼠肝细胞凋亡率较A组明显降低,但较对照组仍明显升高(P 0. 05)。A组大鼠肝脏组织中ERp46蛋白表达水平较对照组显著下降(P 0. 05); B组大鼠肝脏组织中ERp46蛋白表达水平较A组明显上调(P 0. 05),而与对照组表达水平的比较,无显著差异(P 0. 05)。结论利拉鲁肽对NAFLD大鼠肝脏组织具有一定的保护作用,其可能通过提高ERp46的表达水平而发挥减轻NAFLD大鼠胰岛素抵抗和肝脏脂肪变性、减少肝细胞凋亡的作用。     

CK18-M30和内毒素在大鼠非酒精性脂肪肝病中的促进作用

目的探讨细胞角蛋白18-M30片段(CK18-M30)、内毒素在大鼠非酒精性脂肪肝病(NAFLD)转化为非酒精性脂肪性肝炎(NASH)中的促进作用。方法 26只大鼠随机分为3组,对照组(NC组):普通饮食;NAFLD组:高脂饮食喂养8周;NASH组:高脂饮食喂养12周。生化仪测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST);光度法测定血清内毒素(ET);ELISA检测血清IL-18、CK18-M30,RT-PCR分析粪便肠道菌群;行苏木精伊红(HE)染色观察肝脏及末端回肠组织病理。结果 NAFLD及NASH组相比NC组,小肠黏膜结构由轻到重受到破坏。NAFLD组及NASH组大鼠血清ET、CK18-M30、肝脂肪变性程度及NAFLD活动度积分(NAS)、大肠杆菌属计数显著高于NC组,而双歧杆菌属、乳酸杆菌属计数显著低于NC组,差异有统计学意义(P<0.05);NASH组大鼠血清ET、CK18-M30、肝脂肪变性程度及NAS显著高于NAFLD组,差异有统计学意义(P<0.05);NASH组大鼠血清ALT、AST、IL-18显著高于NC组及NAFLD组,差异有统计学意义(P&l...     

中药补气养阴清热活血方抗运动性疲劳的实验研究

目的:探讨中药(非禁用药物)补气养阴清热活血方对抗运动性疲劳的作用。方法:以小鼠为实验动物,分实验组灌服补气养阴清热活血液,运动对照组和正常组灌同等量的生理盐水,每组10只。检测各组小鼠游泳至力竭的时间;力竭游泳后骨骼肌超氧化物歧化酶(superoxidedismutaseSOD)、肌酸激酶、乳酸脱氢酶(lactatedehydrogenaeactivity,LDH)活性和血清肌酸激酶、血清LDH活性;力竭运动结束3h后(恢复期)的血糖浓度、肌糖原和肝糖原的含量。结果:灌服补气养阴清热活血液组小鼠2次力竭游泳时间犤分别为(38.38±6.51),(35.83±8.65)min犦较运动对照组犤分别(28.41±5.38),(23.43±6.84)min犦明显延长,差异显著性意义(t=4.72,4.86P均<0.01);实验组骨骼肌LDH犤(13.37±1.60)μkat犦,SOD犤(49.38±11.77)μkat犦、肌酸激酶(75.47±20.03)μkat犦活性和血清LDH(10.14±2.88)μkat犦,肌酸激酶(30.11±5.61)μkat犦活性较运动对照组犤分别为(1.09±1.83),(43.40±8.88),(44.75±207.14)(14.01±3.16),(91.46±16.50)μkat犦增高,差异有显著性意义(t=2.4～6.3,P均<0.01);实验组力竭游泳3h后肌糖原和肝糖原含量(mg/g)的增加犤分别为(3.91±0.84),(24.87±11.54)犦较运动对照组犤分别为(2.58±0.62),(14.34±7.34)犦明显加快,差异     

两种不同造模方法形成的酒精性肝病小鼠模型比较

目的 明确两种不同造模方法对酒精性肝病模型小鼠的肝脏脂变、炎症及铁沉积的影响。方法 分别采用酒精液体饮食喂养C57BL/6小鼠10 d和8周,分为10 d对照组(对照饮食)、10 d模型组(酒精液体饮食)、8周对照组(对照饮食)、8周模型组(酒精液体饮食),每组10只。造模结束后留取各组小鼠血清及肝脏组织检测。采用苏木精-伊红、油红O、普鲁士蓝染色分别观察小鼠肝脏炎症、脂变、铁沉积情况。依据相应试剂盒说明书检测血清中肝功能生化指标[天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)]、脂质相关生化指标[血清甘油三脂和总胆固醇]、铁代谢相关生化指标[血清铁调素、血清铁及总铁结合力(TIBC)、转铁蛋白饱和度(TS)]。采用Real-time PCR(qPCR)检测肝脏炎症相关基因IL-1β、IL-10以及铁代谢相关基因HAMP的表达。结果 苏木精-伊红染色显示10 d和8周模型组仅少量炎症细胞浸润;油红O染色显示10 d及8周模型组较对照组均出现明显脂变;普鲁士蓝染色显示10 d及8周模型组较对照组均无明显铁沉积。10 d模型组的血清ALT、AST水平以及IL-1β表达均较10 d...     

Yunpi Qushi Jiangzhuo Recipe Alleviates Lipid Deposition and Reduces Liver Damage in Mice with Non-alcoholic Fatty Liver Disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a multifactorial liver metabolic disease, which affects nearly a quarter of the world's population. Yunpi Qushi Jiangzhuo Recipe (QSJZR) is a traditional Chinese medicine compound, which is composed of Amomum kravanh Pierre ex Gagnep, Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf, Prunus armeniaca L.var.ansu Maxim, Salvia miltiorrhiza Bge, Nelumbo nucifera Gaertn, Alisma plantago-aquatica Linn, Polyporus umbellatus (Pers.) Fries, Poria cocos (Schw.) Wolf, and Artemisia capillaris Thunb. QSJZR has a certain therapeutic effect on NAFLD patients, but its specific mechanism is not clear.ObjectiveTo investigate the effect of QSJZR on high-fat diet (HFD)-fed NAFLD mice and its mechanism.MethodsTwenty-four SPF female C57BL/6 J mice (21.0 ± 0.5 g) were randomly divided into normal diet (ND) group, HFD group and QSJZR group. ND group was given basal diet, while the other two groups were given HFD. Meanwhile, each mouse in QSJZR group was given 0.2 mL/day (containing 2.27 g crude drug per mL) QSJZR, ND group and HFD group were given the same amount of normal saline for 13 consecutive weeks. Then, the serum was collected for biochemical assay, and the liver was removed for pathological examination and biochemical analysis.ResultsBody weight and white fat weight of the HFD-induced NAFLD mice significantly decreased after ministration with QSJZR, while liver weight had no significant change. QSJZR also significantly reduced liver and serum triglyceride levels, and alleviated hepatocyte lipid deposition by regulating genes and proteins expression related to lipid metabolism, including AMPK, SREBP1C, CPT1A and ACC. In addition, compared with HFD group, liver malondialdehyde (MDA) content was lower in QSJZR group, while glutathione peroxidase (GPx) content was higher. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were lower in QSJZR group than those in HFD group. Treatment with QSJZR significantly alleviated liver injury by increasing BCL2/BAX protein ratio and down-regulating ASK1/JNK pathway.ConclusionAdministration of QSJZR to NAFLD mice once daily for 13 weeks can decrease lipid levels, and alleviate liver damage. These results suggest that QSJZR might be used to treat NAFLD, although more studies need to be conducted for further verification.     

Therapeutic efficacy of polydatin for nonalcoholic fatty liver disease via regulating inflammatory response in obese mice

Polydatin (PD), a natural precursor of resveratrol, has been used to treat several diseases, such as cardiovascular diseases, hepatic diseases and various cancers. In this study, we aimed to investigate the protective effects and underlying mechanisms of PD on non-alcoholic fatty liver disease (NAFLD) using a high fat induced obese mice model. The studied subjects were randomly divided into a lean group, a high fat diet (HFD) group, and a high fat diet with PD (HFD + PD) group. The results showed that PD reduced the body weights in HFD mice. PD also downregulated the serum levels of triglyceride (TG), low density lipoprotein (LDL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and upregulated high density lipoprotein (HDL). Moreover, PD significantly alleviated hepatocyte steatosis and reduced Gr-1⁺ cells in the liver tissues of HFD mice. The mRNA levels of pro-inflammatory factors, such as monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), S100A8 and S100A9 were significantly decreased in the liver tissues of HFD mice with PD treatment, and the downregulation of MCP-1 and S100A9 protein expressions was also observed. In conclusion, PD had beneficial roles in suppressing lipid accumulation in hepatocytes and anti-inflammatory responses in the liver tissue of obese associated NAFLD.

Polydatin (PD), a natural precursor of resveratrol, has been used to treat several diseases, such as cardiovascular diseases, hepatic diseases and various cancers.     

慢性丙型肝炎肝组织学改变与肝脏瘦素表达的关系

目的研究慢性丙型肝炎(CHC)肝组织学改变与肝脏瘦素表达的关系。方法未经治疗的53例成年CHC患者分为肝脏瘦素阳性组26例和阴性组27例,以单纯非酒精性脂肪性肝病(NAFLD)15例作为对照组,比较各组肝脏瘦素阳性率、肝脏炎症分级、纤维化分期和脂肪变分级有无差异。结果 CHC组脂肪变分级程度轻于NAFLD组(χ2=13.20,P<0.05),但两组分别在脂肪变1级和2级的肝脏瘦素阳性率差异无统计学意义(χ2=2.57,0.04,P均>0.05);两组在轻度炎症和轻度纤维化的瘦素表达阳性率差异有统计学意义,CHC组肝脏瘦素阳性率低于NAFLD组(χ2=4.54,6.86,P均<0.05)。两组CHC的肝脏瘦素阳性率在不同肝脏炎症分级、纤维化分期和是否发生肝脂肪变差异无统计学意义(χ2=0.106,0.846,0.000,P均>0.05),CHC的肝脏瘦素阳性率与肝脏炎症分级、纤维化分期、脂肪变分级和血清HCVRNA水平无明显相关性(P均>0.05)。结论 CHC发生肝脂肪变、肝脏炎症和纤维化程度均与肝脏瘦素表达无明显相关。     

CAP对儿童非酒精性脂肪性肝病的诊断价值研究

[目的]探讨CAP对儿童非酒精性脂肪性肝病(NAFLD)的临床诊断价值.[方法]选择2016年8月至2020年9月本院肝病中心收治的91例NAFLD患儿,均经肝脏组织活检,同时进行受控衰减参数(CAP)检查.另选取30例其他肝病患儿为对照组,经肝活检证实无肝脂肪变性,同时也进行CAP检测.运用儿童NAFLD组织学评分系...     

Diagnostic Performance of 2-D Shear-Wave Elastography with Propagation Maps and Attenuation Imaging in Patients with Non-Alcoholic Fatty Liver Disease

We aimed to investigate the diagnostic performance of new 2-D shear-wave elastography (SWE) with propagation maps and attenuation imaging (ATI) for quantification of fibrosis and steatosis in non-alcoholic fatty liver disease (NAFLD). Consecutive patients with NAFLD and healthy volunteers underwent liver stiffness measurement and steatosis quantification by means of vibration-controlled transient elastography coupled with the controlled attenuation parameter as the reference and by 2-D shear-wave elastography (2-D-SWE) with propagation maps and ATI as the investigational methods. We included 232 participants (164 in the NAFLD group and 68 in the healthy control group): 51.7%/49.3% women/men; mean age, 54.2 ± 15.2 y; mean body mass index, 29.4 ± 6.5 kg/m². Significant correlations were found between 2-D-SWE and vibration-controlled transient elastography (r = 0.71, p < 0.0001) and between ATI and the controlled attenuation parameter (r = 0.72, p < 0.0001). NAFLD-specific 2-D-SWE liver stiffness measurement cutoffs were as follows—F ≥ 2: 7.9 kPa (area under the curve [AUC] = 0.91); F ≥ 3: 10 kPa (AUC = 0.92); and F = 4: 11.4 kPa (AUC = 0.95). For steatosis, the best cutoffs by ATI were as follows—S1 = 0.73 dB/cm/MHz (AUC = 0.86); S2 = 0.76 dB/cm/MHz (AUC = 0.86); and S3 = 0.80 dB/cm/MHz (AUC = 0.83). According to Baveno VI criteria, the optimal 2-D-SWE liver stiffness measurement for diagnosing liver cirrhosis is 15.5 kPa (AUC = 0.94), and for ruling out compensated advanced chronic liver disease it is 9.2 kPa (AUC = 0.92). To conclude, 2-D-SWE with propagation maps and ATI is reliable for quantification of liver fibrosis and steatosis in patients with NAFLD.     

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a major worldwide health problem. Recent studies suggest that the gut microbiota influences NAFLD pathogenesis. Here, a murine model of high-fat diet–induced (HFD-induced) NAFLD was used, and the effects of alterations in the gut microbiota on NAFLD were determined. Mice treated with antibiotics or tempol exhibited altered bile acid composition, with a notable increase in conjugated bile acid metabolites that inhibited intestinal farnesoid X receptor (FXR) signaling. Compared with control mice, animals with intestine-specific Fxr disruption had reduced hepatic triglyceride accumulation in response to a HFD. The decrease in hepatic triglyceride accumulation was mainly due to fewer circulating ceramides, which was in part the result of lower expression of ceramide synthesis genes. The reduction of ceramide levels in the ileum and serum in tempol- or antibiotic-treated mice fed a HFD resulted in downregulation of hepatic SREBP1C and decreased de novo lipogenesis. Administration of C16:0 ceramide to antibiotic-treated mice fed a HFD reversed hepatic steatosis. These studies demonstrate that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota–associated NAFLD development, linking the microbiome, nuclear receptor signaling, and NAFLD. This work suggests that inhibition of intestinal FXR is a potential therapeutic target for NAFLD treatment.     

Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high-fat diet-induced nonalcoholic fatty liver in rats

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease linked to insulin resistance, oxidative stress, and cytokine imbalance. Phosphodiesterase (PDE) inhibitors have shown remarkable antioxidant and anti-inflammatory potential in different disease sets including liver diseases. This study aimed to compare the ameliorative effect of different PDE inhibitors on a high-fat diet (HFD)-induced NAFLD. Male Wistar rats were fed a HFD for 16 weeks to induce NAFLD, and then, oral treatments of a vehicle or different PDE inhibitors (pentoxifylline (50 mg/kg), cilostazol (20 mg/kg), or sildenafil (5 mg/kg)) were started in the last four weeks and given on a daily basis. Rats’ body composition and liver indices were recorded. Serum levels of liver enzymes, glucose, insulin, bilirubin, total cholesterol, triglycerides, and nitric oxide were measured. Liver tissues were used for histopathological examination and detecting oxidative stress and inflammatory markers. Results showed that different PDE inhibitors exhibited different efficacy against liver injury and metabolic disorders associated with HFD-induced NAFLD in rodents evident by different strength-ameliorated effects on the aforementioned parameters. Compared to cilostazol and sildenafil, insulin resistance, hepatic oxidative stress, and inflammatory markers were significantly reduced by pentoxifylline treatment. Furthermore, pentoxifylline nearly completely reversed hepatocyte steatosis and exhibited superior rectifying effect on the rats’ liver status compared with other PDE inhibitors. This investigation highlighted the potential role of PDE inhibitors in NAFLD treatment. Pentoxifylline had the most remarkable ameliorative effects against NAFLD, while sildenafil was the least effective.     

添加短链脂肪酸的TPN对术后化疗大鼠结肠粘膜细胞增殖作用的研究

目的探讨添加短链脂肪酸(SCFAs)的全肠外营养(TPN)对术后化疗大鼠结肠粘膜细胞增殖作用的影响。方法30只SD大鼠在无渣饮食2d后建立TPN和结肠吻合模型。术后随机分为TPN对照组(对照组)、化疗+TPN组(化疗组)、化疗+TPN+SCFAs组(SCFAs组),每组10只。进行实验5 d,术后第6 d留取标本采用流式细胞术分析结肠粘膜细胞周期,观察其增殖情况。结果化疗组结肠粘膜细胞增殖期百分比(6.23±2.75)%显著低于对照组[(9.81±2.78)%,P=0.014]和SCFAs组[(11.57±3.54)%,P=0.001];化疗组结肠粘膜细胞的增殖指数(11.87±2.61)%显著低于其他2组[(20.25±7.22)%,P=0.002;(19.70±5.12)%,P=0.003]。结论添加SCFAs的TPN能促进术后化疗大鼠结肠粘膜细胞的增殖。     

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients

Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.     

超声衰减成像技术评价肝脂肪变性的相关因素分析

目的探讨影响超声衰减系数（AC）变化的相关因素,并评估衰减成像（ATI）技术对非酒精性脂肪性肝病（NAFLD）定量诊断的临床实用性及测量的可重复性。 方法选取2019年9月至2020年12月在哈尔滨医科大学附属第一医院使用超声的ATI技术进行肝检测的114例受试者（NAFLD组56例,健康对照组58例）,分别获得二维超声和AC,同时收集患者相应的临床资料、血生化检测指标等,通过多因素线性回归分析确定AC的独立影响因素。使用常规二维超声检查对所有研究对象的肝脂肪变性程度进行四分制评分（S0~S3组）,采用方差分析检验各组间AC的差异性,使用Spearman相关分析方法评估AC与肝脂肪变性程度的相关性,并计算组内相关系数（ICC）,评估2名操作者间（AC-1组和AC-2组）ATI测量的可重复性。 结果多因素线性回归分析显示体质量指数（BMI）、肝脂肪变性程度是AC的独立影响因素（β=0.007,95%CI：0.001~0.013,P=0.017;β=0.083,95%CI：0.070~0.095,P＜0.001）。NAFLD组AC显著高于健康对照组［AC-1组：（0.716±0.098）dB/（cm·MHz）vs（0.539±0.058）dB/（cm·MHz）;AC-2组：（0.699±0.102）dB/（cm·MHz）vs（0.542±0.053）dB/（cm·MHz）］,且随着肝脂肪变性程度的加重,AC逐渐升高［S0组（58例）AC为（0.539±0.058）dB/（cm·MHz）,S1组（23例）AC为（0.640±0.063）dB/（cm·MHz）,S2组（20例）AC为（0.718±0.050）dB/（cm·MHz）,S3组（13例）AC为（0.845±0.059）dB/（cm·MHz）;F=122.27,P＜0.001］。AC与肝脂肪变性程度存在较强的相关性（r=0.840;P＜0.001）。不同肝脂肪变性程度AC的组内相关系数（ICC）分别为0.816（95%CI：0.708~0.881）、0.886（95%CI：0.301~0.967）、0.876（95%CI：0.479~0.960）、0.939（95%CI：0.819~0.981）,P均＜0.001。 结论AC与BMI、肝脂肪变性程度显著相关,且ATI技术的操作者间可重复性极好,结果较为稳定,有助于早期发现脂肪肝并对脂肪肝严重程度进行评估。