NLRP3炎性小体与心血管疾病的研究进展

炎性小体(inflammasome)是一种多蛋白复合物,主要由识别炎症的胞浆型模式识别受体(PRRs)、接头蛋白凋亡相关斑点样蛋白(ASC)和效应蛋白前半胱天冬酶-1(pro-caspase-1)三部分组成.炎性小体的激活过程中最主要的步骤是白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)等炎性因子的成熟...     

利拉鲁肽对糖尿病肾病大鼠NLRP3表达的影响

目的 探讨利拉鲁肽是否通过抑制NLRP3炎症小体（The NLRP3 inflammasome,NLRP3）的活化在糖尿病肾病（Diabetic Nephropathy,DKD）中发挥肾脏保护作用。方法 Wistar品系大鼠22只,雄性,4周龄,采用单纯随机抽样方法分为正常对照组（NC组,n=6）、利拉鲁肽干预DKD组（LIR组,n=8）和生理盐水干预DKD组（NS组,n=8）。LIR组予利拉鲁肽200μg•kg-1•d-1皮下注射,NS组予等体积的生理盐水皮下注射,NC组不做任何处理,共治疗4周。治疗结束后检测大鼠体重、24h尿总蛋白定量（Urinary total protein,UTP）、空腹血糖（Fasting blood-glucose,FPG）、甘油三酯（Transformational Grammar,TG）、胆固醇(Temperature Coefficient,TC)、血尿素氮（Blood Urea Nitrogen,BUN）、血肌酐（Silicon ControlledRectifier,Scr）等生化指标,各组大鼠肾组织苏木素-伊红染色(HE),光镜下观察肾组织病理形态学改变,Western-blot检测肾组织中NLRP3炎症小体蛋白表达,Elisa检测血清白介素-18（Interleukin - 18,IL-18）及血清白介素-1β（IL-1β）的水平。结果 利拉鲁肽组大鼠FBG、UTP、BUN、Scr、TC、TG等生化指标水平较生理盐水组改善;肾脏组织病理切片提示正常对照组肾小球、肾小管结构正常,生理盐水组可见肾小球体积增大、 结构紊乱,系膜外基质增多,基底膜增厚明显,利拉鲁肽组大鼠肾脏病理变化减轻;Western-blot检测提示经过利拉鲁肽的干预,NLRP3炎症小体的蛋白表达明显低于生理盐水组;Elisa检测提示生理盐水组IL-18、IL-1β水平明显增加,经利拉鲁肽干预后,IL-18、IL-1β水平下降。结论 利拉鲁肽可以改变糖尿病肾病大鼠的疾病进程,这可能与利拉鲁肽抑制NLRP3炎症小体的激活有关。     

NASH患者外周血单个核细胞TXNIP/NLRP3水平变化及其临床意义探讨

目的 探讨非酒精性脂肪性肝炎(NASH)患者外周血单个核细胞(PBMCs)硫氧还蛋白互作蛋白(TXNIP)/NOD样受体家族含pyrin结构域蛋白3(NLRP3)水平变化及其临床意义。方法 2019年1月～2021年1月我院收治的150例NASH患者和同期体检的单纯性脂肪肝患者45例,取外周血分离PBMCs,并检测TXNIP/NLRP3 mRNA。对NASH患者行两次肝穿刺活检,将肝组织病变程度分为轻度、中度和重度及进展和无进展组。结果 NASH患者血清ALT和AST水平分别为(72.2±6.9)U/L和(61.8±5.1)U/L,显著高于单纯性脂肪肝组【分别为(33.4±4.0)U/L和(31.3±3.1)U/L,P<0.05】;NASH组PBMCs TXNIP mRNA、NLRP3 mRNA和TXNIP/NLRP3比值分别为(1.9±0.1)、(1.5±0.1)和(1.3±0.1),显著高于单纯性脂肪肝组【分别为(0.7±0.1)、(0.6±0.1)和(1.1±0.1),P<0.05】;33例重度NASH组PBMCs TXNIP mRNA、NLRP3 mRNA和TXNI...     

Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

Background and AimsThe effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms.MethodsMice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs).ResultsGinsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1β, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration.ConclusionsGinsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.