不同输注途径移植骨髓间充质干细胞对阿霉素肾病大鼠疗效初探

【摘要】目的探索骨髓间充质干细胞（BMSCs）经不同输注方式移植入阿霉素慢性肾病大鼠体内对肾损伤的影响。方法SD大鼠左侧肾切除后以2.5mg/kg剂量给大鼠尾静脉注射阿霉素,1次/周,连续2次,慢性肾病模型成功后,将成模大鼠36只随机均分为3组：阿霉素慢性肾病对照（ADR）组、干细胞经肾动脉移植（M-A）组、干细胞经外周静脉移植（M-V）组,另选12只正常大鼠设正常对照（N）组。BMSCs经体外培养后,以2×10⁶个/mL经肾动脉注射到M-A组大鼠体内,2×10⁶个/mL经尾静脉注射到M-V组大鼠体内,2周后再次同样方法注射等量BMSCs。检测移植当周、移植后1周、2周大鼠血尿素氮、血肌酐、24h尿蛋白、24h尿微量蛋白,末次注射干细胞后第1周于激光聚焦显微镜下观察大鼠肾脏病理和干细胞在肾脏内分布情况。结果M-A组、M-V组和ADR组在各观察时点血尿素氮、血肌酐、24h尿蛋白总量、24h尿微量蛋白均明显高于N组（P＜0.01）。移植后1、2周M-A组的24h尿微量蛋白低于ADR组（P＜0.01）,且M-A组的血肌酐较ADR组和M-V组均降低（P＜0.01）。移植后1周,M-A组24h尿蛋白、24h尿微量蛋白明显低于M-V组（P＜0.01）;但2周时尿蛋白和微量蛋白与M-V组的差异无统计学意义。结论BMSCs移植可以改善阿霉素慢性肾病的肾损伤情况,在BMSCs移植后一段时间,BMSCs经肾动脉移植的效果优于经外周静脉移植。     

基于ROS-NLRP3炎症小体介导的细胞焦亡探究利拉鲁肽对糖尿病肾病大鼠肾损伤的保护作用

目的 探究利拉鲁肽对糖尿病肾病大鼠的作用及其调控机制。方法 采取多次小剂量ip链脲佐菌素40 mg/kg构建糖尿病肾病大鼠模型,分为模型组、利拉鲁肽组、活性氧簇（ROS）抑制剂（NAC）组、利拉鲁肽+NAC组,另设置对照组,每组10只。利拉鲁肽组大鼠sc 200μg/(kg·d)的利拉鲁肽;NAC组大鼠ip 20 mg/(kg·d)的NAC;利拉鲁肽+NAC组大鼠sc 200μg/(kg·d)的利拉鲁肽的同时ip 20 mg/(kg·d)的NAC;对照组和模型组大鼠sc等量的生理盐水,1次/d,连续治疗4周。全自动分析仪检测24 h尿微量蛋白排泄率（MAER）;血糖仪测定空腹血糖（FBG）;试剂盒检测血清肌酐（Scr）、尿素氮（BUN）水平;HE染色、Masson染色观察肾组织病理变化;二氢乙锭（DHE）荧光探针检测肾组织活性氧（ROS）水平;化学比色法检测肾组织丙二醛（MDA）含量、谷胱甘肽过氧化物酶（GSH）和超氧化物歧化酶（SOD）活性;Western blotting检测肾组织NOD样受体蛋白3(NLRP3)炎症小体和焦亡相关蛋白表达。结果 与模型组相比,利拉鲁肽组和NAC组大...     

银杏叶提取物通过miR-145/FOXO1轴对实验性肾功能衰竭大鼠肾脏损伤的影响

目的：探讨银杏叶提取物（GBE）对慢性肾功能衰竭（CRF）大鼠肾损伤的影响及潜在的分子机制。方法：SD大鼠采用5/6肾切除术构建CRF模型，并分为模型（model）组、GBE组（100 mg/kg）、GBE+Agomir-NC组、GBE+Agomir-145组，每组12只；另取12只为假手术（sham）组，仅暴露肾脏，不进行肾脏切除。GBE组大鼠每日给予GBE100 mg/kg灌胃，1次/d，连续4周；GBE+AgomirNC组和GBE+Agomir-145组大鼠每日给予GBE100 mg/kg灌胃，然后每3 d一次分别通过尾静脉注射Agomir-NC和Agomir-145，连续4周；sham组和model组灌胃和尾静脉注射等量生理盐水。观察大鼠的一般状态，检测大鼠肾功能指标[24 h尿微量白蛋白（24 h UAlb）、血尿素氮（BUN）、血肌酐（SCr）]和氧化应激指标[丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSHPx）]，采用Masson染色观察肾组织纤维化情况，采用实时荧光定量PCR(RT-qPCR)检测肾组织microRNA-145(miR-145)、...     

Klotho蛋白对肾缺血再灌注大鼠急性肾损伤及纤维化的保护作用

目的 探讨Klotho蛋白在缺血再灌注（I/R）大鼠引起的急性肾损伤及纤维化进程中的作用。方法 60只健康雄性SD大鼠按随机数字表法分为假手术组（Sham组）、肾脏缺血再灌注组（I/R组）和Klotho蛋白干预组（I/R+Kl组），每组20只。I/R组采用夹闭右侧肾蒂40 min再灌注法建立肾缺血再灌注急性肾损伤模型。Sham组游离出右侧肾动脉，但不夹闭右侧肾蒂，暴露40 min后缝合腹腔。I/R+Kl组手术方法同I/R组，造模成功后，腹腔注射Klotho蛋白（0.01 mg/kg）。3组分别于造模成功后第1、7、14、28天收集大鼠血、肾组织标本，分别检测大鼠血肌酐（Scr）、尿素氮（BUN）水平；HE染色观察肾组织损伤情况，Masson染色观察肾纤维化情况，酶联免疫吸附试验（ELISA）检测血清及肾组织Klotho蛋白水平，Western blot法检测肾脏组织Klotho蛋白的表达。结果 与Sham组比较，I/R组及I/R+Kl组血Scr及BUN水平均升高（P<0.05），与I/R+Kl组比较，I/R组各时间点血Scr及BUN水平均升高（P<0.05）。HE染色结果显...     

金雀异黄素对肾小管间质纤维化模型大鼠肾组织DDR1、bFGF表达的影响

目的 探讨DDR1在肾小管损伤及间质纤维化过程中的表达以及金雀异黄素在肾小管损伤及间质纤维化过程中对肾脏的保护作用及可能机制.方法 采用单侧输尿管结扎致肾间质纤维化大鼠模型,将45只大鼠随机分为三组:假手术组、模型组、金雀异黄素干预组,分别于术后7d、14d、21d每组各处死5只大鼠,收集血清测定尿素氮(BUN)、血肌酐(Scr)水平,结扎侧肾组织行HE染色观察肾脏病理变化,Masson染色分析肾间质纤维化程度,免疫组化半定量检测各组大鼠肾组织DDR1、bFGF的表达.结果 模型组DDR1、bFGF表达及肾间质纤维化程度明显高于假手术组,BUN、Scr水平显著升高(P＜0.01);金雀异黄素干预组DDR1、bFGF表达及肾间质纤维化程度较模型组明显降低(P如.01或0.05),部分时间段BUN、Scr水平有所下降(P＜0.05).结论 金雀异黄素可能通过降低DDR1及bFGF的表达而减轻肾小管损伤及间质纤维化程度.     

肾茶对UUO大鼠肾组织FaS、FasL表达的影响

目的：探讨肾荼对UUO大鼠肾组织Fas（Fas蛋白）、FasL（FasL蛋白）表达的影响。方法：将清洁级SD大鼠随机分为模型组、假手术组、肾茶组。模型组、肾茶组分离、结扎左侧榆尿管,并离断;假手术组只分离左侧榆尿管,不结扎、离断。肾茶组给予剂量为8g／kg的肾茶煎剂灌胃,模型组、假手术组给予等体积的生理盐水灌胃,分别于术后3d,7d,14d在每组大鼠中随机取8只,麻醉后心脏取血测定血尿素氮、血肌酐,处死大鼠,摘取左侧（术侧）肾脏后采用免疫组化方法检测大鼠肾组织中Fas和FasL的表达。结果：同模型组相比,术后3d、7d、14d肾茶组血尿素氮、血肌酐下降,肾问质纤维化程度减轻,Fas、FasL表达下调,各组间差异有统计学意义（P〈0．05）。结论：肾茶能够延缓单侧输尿管结扎大鼠肾间质纤维化程度,其疗效可能是使进行性纤维化的肾组织Fas、FasL的表达降低。     

中药芪红合剂对肾间质纤维化模型大鼠肾组织中PAI-1表达的影响

目的:探讨中药芪红合剂对肾问质纤维化模型大鼠肾组织中纤溶酶原激活物抑制剂-1(PAI-1)表达的影响,及其对肾间质纤维化的作用机制.方法:采用单侧输尿管结扎(UUO)致肾问质纤维化的动物模型,40只雄性Wistar大鼠随机分为4组:假手术组(A组)、手术模型组(B组)、芪红合剂组(C组)、依那普利组(D组).术后14 d处死各组大鼠.收集血清、测定血肌酐(Scr)、尿素氮(BUN)水平,取结扎侧肾组织分别用HE、Masson染色,采用免疫组化检测肾组织中纤溶酶原激活物抑制剂-1(PAI-1)的表达,并用计算机图像分析系统进行分析.结果:模型组大鼠肾组织中PAI-1的表达较假手术组显著升高.两治疗组较模型组明显降低.模型组大鼠血肌酐、尿素氮水平较假手术组明显增高、两治疗组较模型组显著下降.结论:中药芪红合剂可降低大鼠血尿素氮、血肌酐水平,并可通过抑制纤溶酶原激活物抑制剂-1(PAI-1)的表达,而起到减轻肾间质纤维化病变程度的作用,推测其抑制PAI-1表达上调的作用可能是其抗肾间质纤维化的作用机制之一.     

甘草酸对慢性肾脏病大鼠心肌HMGB1/TLR4/NF-κB/HIF-1α信号通路的影响

目的 探讨应用甘草酸（Gly）治疗时对慢性肾脏病（CKD）大鼠心室肌高迁移率族蛋白B1/Toll样受体4/核因子κB/缺氧诱导因子1α(HMGB1/TLR4/NF-κB/HIF-1α)信号通路的影响。方法 将38只Wistar大鼠按随机数字表法分为4组：假手术（Sham）组、Sham+Gly组、CKD组、CKD+Gly组，5/6肾切除制备CKD模型，Gly腹腔注射给药（80 mg/kg）。4周后行血流动力学及心脏彩超观察各组大鼠心脏功能；心室取血检测生化指标；心肌组织取材检测HMGB1、TLR4、NF-κB、HIF-1α蛋白表达的变化。结果 与Sham组相比，CKD组肌酐、尿酸、尿素氮和血清镁水平增高（P<0.05），血压升高，舒张期室间隔厚度、收缩期左心室内径增加，左心室射血分数降低，E/A比值降低，肺动脉血流加速时间延长（P<0.05）;HE染色可见心肌细胞肥大，Masson染色见心肌纤维化程度增加（P<0.05），心肌组织HMGB1、NF-κB、HIF-1α蛋白表达水平上调（P<0.05）。与CKD组相比，CKD+Gly组收缩期室间隔厚度增加，左心室射血分...     

骨髓间充质干细胞移植对慢性胰腺炎大鼠模型胰腺纤维化的影响

摘要： 目的 观察骨髓间充质干细胞 （BMSCs） 移植对慢性胰腺炎大鼠模型胰腺纤维化的影响, 并探讨其作用机制。方法 将 30 只健康雄性 SD 大鼠随机分为对照组、 模型组和移植组, 每组 10 只。模型组采用胆胰管逆行注射油酸法制备大鼠慢性胰腺炎模型, 对照组以同样方式仅注射相同体积生理盐水, 移植组在造模后 1 周和 5 周经尾静脉注射 BMSCs。分别于造模后第 1、 4 和 8 周称量 3 组大鼠体质量, 于第 8 周后剖杀动物, 取胰腺组织行 HE 染色和饱和苦味酸-天狼猩红染色观察胰腺组织病理学改变并评分, 采用 ELISA 法检测胰腺组织转化生长因子 （TGF） -β1、 Ⅰ型胶原和Ⅲ型胶原含量。结果 造模后第 4 周, 模型组和移植组大鼠体质量均低于对照组 （P＜0.05）, 模型组与移植组间差异无统计学意义（P＞0.05）; 至第 8 周, 模型组和移植组大鼠体质量仍低于对照组, 而移植组高于模型组（P＜0.05）。模型组大鼠胰腺组织纤维化评分升高、 TGF-β1、 Ⅰ型胶原和Ⅲ型胶原含量均高于对照组和移植组（P < 0.05）; 移植组胰腺组织纤维化评分高于对照组, TGF-β1、 Ⅰ型胶原和Ⅲ型胶原含量与对照组差异无统计学意义。结论 BMSCs 移植能减少慢性胰腺炎大鼠胶原分泌, 降低胰腺纤维化程度, 其机制可能与抑制 TGF-β1分泌有关     

电针协同BMSCs移植治疗对脑出血大鼠MAP-2表达的影响

目的探讨电针（Ea）协同骨髓间充质干细胞（BMSCs）移植治疗对脑出血大鼠微管相关蛋白（MAP-2）表达的影响。方法采用大鼠脑尾核壳注射胶原酶与肝素制备脑出血动物模型,并分为Ea组、Ea—BMSCs组、BMSCs组和生理盐水（NS）组．分别给予Ea刺激、Ea刺激协同BMSCs移植、BMSCs移植和注射生理盐水,免疫组织化学方法观察各组在不同时间点MAP-2的表达。结果MAP-2表达在NS组各时间点之间无明显差异,在Ea组、BMSCs组和Ea—BMSCs组于第5天时达高峰。各组同-时间点比较,Ea组（1d除外）、BMSCs组和Ea-BMSCs组的MAP-2表达高于NS组（P〈0．05）,Ea—BMSCs组高于Ea组及BMSCs组（P〈0．05）。结论Ea协同BMSCs移植较单纯Ea刺激或BMSCs移植更能促进脑出血大鼠MAP-2蛋白表达。提示Ea协同BMSCs移植有助于脑组织结构重塑。     

Renal cellular hypoxia in adenine‐induced chronic kidney disease

We determined whether adenine‐induced chronic kidney disease (CKD) in rats is associated with renal tissue hypoxia. Adenine (100 mg) or its vehicle was administered to male Sprague‐Dawley rats, daily by oral gavage, over a 15‐day period. Renal function was assessed before, and 7 and 14 days after, adenine treatment commenced, by collection of a 24‐hour urine sample and a blood sample from the tail vein. On day 15, arterial pressure was measured in conscious rats via the tail artery. Renal tissue hypoxia was then assessed by pimonidazole adduct immunohistochemistry and fibrosis was assessed by staining tissue with picrosirius red and Masson's trichrome. CKD was evident within 7 days of commencing adenine treatment, as demonstrated by increased urinary albumin to creatinine ratio (30 ± 12‐fold). By day 14 of adenine treatment plasma creatinine concentration was more than 7‐fold greater, and plasma urea more than 5‐fold greater, than their baseline levels. On day 15, adenine‐treated rats had slightly elevated mean arterial pressure (8 mmHg), anaemia and renomegaly. Kidneys of adenine‐treated rats were characterised by the presence of tubular casts, dilated tubules, expansion of the interstitial space, accumulation of collagen, and tubulointerstitial hypoxia. Pimonidazole staining (hypoxia) co‐localised with fibrosis and was present in both patent and occluded tubules. We conclude that renal tissue hypoxia develops rapidly in adenine‐induced CKD. This model, therefore, should prove useful for examination of the temporal and spatial relationships between tubulointerstitial hypoxia and the development of CKD, and thus the testing of the ‘chronic hypoxia hypothesis’.     

Hederagenin inhibits high glucose-induced fibrosis in human renal cells by suppression of NLRP3 inflammasome activation through reducing cathepsin B expression

Diabetic nephropathy is a major complication of diabetes mellitus and is related to dysfunction of renal cells. Hederagenin is a triterpenoid saponin from some Chinese herbs with anti-inflammatory and anti-diabetic activities. However, its role in diabetic nephropathy progression is still obscure. This study aimed to explore the effects of hederagenin on renal cell dysfunction in vitro. Human renal mesangial cells (HRMCs) and human renal proximal tubular epithelial cells (HRPTEpiCs) were cultured under high glucose (HG) conditions to mimic diabetic nephropathy-like injury. Cell proliferation was evaluated by CCK-8. mRNA and protein levels were determined by qRT-PCR and western blotting, respectively. The secretion levels of fibrosis-related biomarkers were analyzed by ELISA. Results showed that hederagenin reduced HG-induced proliferation increase in HRMCs and HRPTEpiCs. Hederagenin attenuated HG-induced increase in mRNA and protein expression of NLRP3, ASC, and IL-1β. Hederagenin also suppressed HG-induced increase in mRNA and secretion levels of FN, Col. IV, PAI-1, and TGF-β1. NLRP3 inhibitor MCC950 attenuated HG-induced fibrosis of renal cells, and its activator nigericin reversed the suppressive effect of hederagenin on HG-induced fibrosis. Bioinformatics analysis predicted cathepsin B (CTSB) as a target of hederagenin to modulate NOD-like receptor (NLR) pathway. Hederagenin decreased CTSB level, and CTSB overexpression reversed the suppressive effect of hederagenin on HG-induced NLRP3 inflammasome activation and fibrosis in HRMCs and HRPTEpiCs. In conclusion, hederagenin attenuates HG-induced fibrosis of renal cells by inhibiting NLRP3 inflammasome activation via reducing CTSB expression, indicating a therapeutic potential of hederagenin in diabetic nephropathy.     

昆布多糖对肾纤维化大鼠肾组织内质网应激的保护作用

目的研究昆布多糖对肾纤维化大鼠肾组织内质网应激(ERS)分子伴侣GRP78、GRP94蛋白表达的影响。方法采用单侧输尿管梗阻(UUO)诱导大鼠肾间质纤维化的动物模型,将大鼠随机分为假手术组、模型组、依那普利组、昆布多糖高、中、低剂量组。术后第7天处死大鼠,收集血清测定肌酐(Scr)、尿素氮(BUN)水平。采用Western免疫印迹法检测大鼠肾组织GRP78、GRP94的蛋白表达;采用HE、Masson染色检测肾小管损伤及肾间质纤维化程度。结果各治疗组与模型组比较大鼠肾小管间质损伤指数、肾间质纤维化程度、血清Scr、BUN水平及肾组织GRP78、GRP94蛋白表达有差异(P<0.05;P<0.01),昆布多糖与依那普利组比较,大鼠肾组织GRP78、GRP94表达升高(P<0.05),肾小管间质损伤及肾间质纤维化程度明显降低(P<0.05),肾功能Scr、BUN明显降低(P<0.05)。结论UUO早期昆布多糖可能通过上调ERS分子伴侣GRP78、GRP94蛋白表达,协助变性蛋白进行重新折叠、装配及跨膜转运,抑制未折叠蛋白反应,阻断ERS应激信号传导通路,从而减轻肾间质纤维化的发生和发展。     

Triptolide improves myocardial fibrosis in rats through inhibition of nuclear factor kappa B and NLR family pyrin domain containing 3 inflammasome pathway

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM-1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.     

The NLRP3 inflammasome is a potential target of ozone therapy aiming to ease chronic renal inflammation in chronic kidney disease

Ozone therapy is an effective medical treatment for various diseases. A previous study has demonstrated its reno-protective effect in chronic kidney disease (CKD), but the mechanism involved is not completely known. This study produced the 5/6 nephrectomized CKD rat model and investigated whether the reno-protective effect of ozone therapy was achieved by its anti-inflammatory property through the modulation of the NLRP3 inflammasome. The results showed that ozone therapy at a low concentration improved renal function and ameliorated renal morphological injury in 5/6 nephrectomized rats. The expression of NLRP3, ASC, and caspase-1-p10 in the kidney of these rats was simultaneously lowered by ozone therapy. Moreover, renal inflammation caused by IL-1β was significantly alleviated by ozone therapy. The Pearson correlation analysis indicated that the protein level of IL-1β was positively correlated with renal injury scores. Taken together, these results indicated that ozone therapy might reduce sterile renal inflammation and slow down CKD progression through the modulation of the NLRP3 inflammasome in 5/6 nephrectomized rats.     

肾性高血压大鼠胰岛素抵抗与肾间质纤维化相关研究

目的 从肾素.血管紧张素系统(RAS)角度初步探讨胰岛素抵抗(IR)对肾性高血压大鼠肾间质纤维化的影响.方法 SD大鼠行"两肾一夹"手术后随机分为蔗糖喂养组和对照组,蔗糖喂养组蔗糖喂养,对照组正常饲养,18周后处理.于处理前1日测定24 h尿蛋白定量;处理日测定2组血浆空腹血糖、胰岛素、胰岛素敏感指数、肾素、血管紧张素Ⅱ、醛固酮、尿素氮和肌酐水平.结果 与时照组相比,蔗糖喂养组空腹胰岛素水平明显增高(P<0.01),胰岛素敏感指数水平明显降低(P<0.01),血浆肾素、血管紧张素Ⅱ、醛固酮、尿素氮和肌酐水平及24 h尿蛋白定量均明显高于对照组(P<0.01).相关分析显示,24 h尿蛋白定量与血浆空腹胰岛素、胰岛素敏感指数、醛固酮及尿素氮水平呈明显相关.结论 IR状态能够加速肾性高血压大鼠肾间质纤维化的损害,除与血压升高、胰岛素的直接促增殖作用有关外,还可能与HIS引起的肾组织局部RAS的激活有关.     

Ergosta-4,6,8(14),22-tetraen-3-one isolated from Polyporus umbellatus prevents early renal injury in aristolochic acid-induced nephropathy rats

Objectives Aristolochic acid (AA) nephropathy, first reported as Chinese herbs nephropathy, is a rapidly progressive tubulointerstitial nephropathy that results in severe anemia, interstitial fibrosis and end‐stage renal disease. Tubulointerstitial injury was studied in a rat model of AA nephropathy to determine whether ergosta‐4,6,8(14),22‐tetraen‐3‐one (ergone) treatment prevents early renal injury in rats with aristolochic acid I‐induced nephropathy. Methods Early renal injury via renal interstitial fibrosis was induced in rats by administration of aristolochic acid I (AAI) solution intragastrically for 8 weeks. Ninety‐six rats were randomly divided into four groups (n = 24/group): (1) control (2) AAI (3) AAI + ergone (10 mg/kg) and (4) AAI + ergone (20 mg/kg). Blood and urine samples were collected and rat were sacrificed for histological assessment of the kidneys on at the end of weeks 2, 4, 6 and 8. Key findings AAI caused progressive elevation of blood urea nitrogen, creatinine, potassium, sodium, chlorine, proteinuria and urinary N‐acetyl‐β‐D‐glucosaminidase (NAG). Ergone suppressed elevation of blood urea, nitrogen, creatinine, proteinuria and urinary NAG to some degree, but the AAI–ergone‐treated group did not differ from AAI‐treated group for body weight, serum potassium, sodium and chlorine. The progress of the lesions in the kidney after AAI administration was also observed by histopathological examinations, but kidneys from rats of AAI–ergone‐treated group displayed fewer lesions. Conclusions Ergone treatment conferred protection against early renal injury in a rat model of AA nephropathy. Early administration of ergone may prevent the progression of renal injury and the subsequent renal fibrosis in AA nephropathy.     

番茄红素对肾脏缺血再灌注损伤大鼠的保护作用

目的探究番茄红素(LP)通过抑制硫氧还蛋白相互作用蛋白/NOD样受体热蛋白结构域相关蛋白3(TXNIP∕NLRP3)信号通路保护大鼠肾脏缺血再灌注损伤(IRI)。方法 100只大鼠随机分为对照组(n=25)、模型组(n=25)及低剂量实验组(n=25)、高剂量实验组(n=25)。模型组及低/高剂量实验组均采用右侧肾切除伴左侧肾血管结扎45 min再灌注24 h的方法建立肾IRI大鼠模型。造模后,低、高剂量实验组灌胃10,20 mg·kg-1·d-1 LP,对照组与模型组灌胃等量生理盐水,连续干预4周。用全自动生化分析仪检测大鼠血清尿素氮(BUN)、血肌酐(SCr)及尿酸(UA)含量;用苏木精-伊红(HE)染色观察大鼠肾脏病理学变化;用蛋白质印迹法检测各组大鼠肾组织中TXNIP和NLRP3蛋白表达;用酶联免疫吸附实验(ELISA)法检测血清肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)及细胞间黏附分子-1(ICAM-1)水平。结果对照组、模型组、低、高剂量实验组大鼠血清BUN水平分别为(5.97±1.36),(24.73±3.54),(15.33±3.12),(9.62±2.57)mmol·L-1;SCr水平分别为(24.38±3.52),(61.36±7.21),(43.26±5.83),(32.48±4.35)μmol·L-1;UA水平分别为(56.78±9.32),(113.56±20.12),(86.38±19.22),(69.21±12.02)mmol·L-1;肾组织TXNIP蛋白相对表达量分别为0.14±0.05,0.93±0.07,0.51±0.12,0.32±0.09;NLRP3蛋白相对表达量分别为0.09±0.06,0.96±0.04,0.38±0.11,0.25±0.06,差异均有统计学意义(均P<0.05)。结论 LP可改善肾IRI大鼠肾组织损伤,抑制炎性反应,同时改善肾功能,其作用机制可能与抑制TXNIP∕NLRP3通路的信号转导有关。     

水飞蓟宾调控NF-κB通路和NLRP3炎症小体改善脂多糖所致大鼠急性肾损伤

目的: 探讨水飞蓟宾(silybin,SB)对脂多糖(lipopolysaccharide,LPS)所致大鼠急性肾损伤的保护作用及机制。方法: 选用45只雄性SD大鼠,随机分为空白组(CTRL)、模型组(LPS)和水飞蓟宾给药组(LPS+SB)。LPS+SB组连续5 d灌胃给药(每日100 mg·kg^-1),其他组采用等体积0.9%氯化钠溶液同步处理,第5天时LPS组与LPS+SB组灌胃给药2 h后腹腔注射LPS(10 mg·kg^-1),CTRL组采用0.9%氯化钠溶液同步处理,8 h后经腹主动脉取血并收集肾脏组织;ELISA试剂盒检测血清、TNF-α和IL-6水平变化;生化试剂盒检测肌酐和尿素氮指标;HE染色观察肾组织病理学变化;Western blot法检测肾组织核转录因子-κB(NF-κB)、Nod样受体蛋白3(NLRP3)和相关蛋白的表达情况。结果: SB能够明显降低血清和组织中TNF-α和IL-6炎症因子水平,显著改善大鼠肾脏功能,减轻肾组织病理性损伤;Western blot结果表明SB可以抑制LPS所致NLRP3炎症相关蛋白的表达和NF-κB通路的激活。结论: SB可有效改善LPS所致大鼠肾损伤,作用机制可能与抑制NLRP3炎症小体激活以及调控NF-κB信号通路有关。