连黄降浊颗粒对自发性高血压大鼠肾脏功能和结构的保护作用

目的：观察连黄降浊颗粒对自发性高血压（SHR）大鼠肾脏功能和结构的保护作用。方法：将29只SHR随机分为模型组、西药对照组（对照组）、连黄降浊颗粒低剂量组（低剂量组）、连黄降浊颗粒高剂量组（高剂量组）。分别给于相应浓度和剂量的药物灌胃12周,观察大鼠的血压、尿蛋白、肾功能和血管紧张素Ⅱ（AngⅡ）、内皮素（ET）水平以及肾组织病理改变;并用半定量方法评价肾小球硬化程度、肾小管损伤程度及肾间质纤维化程度,用ELISA测定肾皮质转化生长因子-β1（TGF-β1）的蛋白定量。结果：连黄降浊颗粒能减少SHR尿蛋白、降低血压、改善肾功能、抑制AngⅡ和ET的合成,减轻肾脏病理损害,减轻肾小球硬化、肾小管损伤及肾间质纤维化程度,抑制肾脏TGF-β1表达,其效果优于苯那普利。结论：连黄降浊颗粒具有保护SHR肾功能和减轻肾脏病理损害的作用,其机制可能与减少尿蛋白、降低血压、抑制AngⅡ和ET的合成、减轻肾小球硬化和肾间质纤维化、抑制肾脏TGF-β1表达等有关。     

骨髓间充质干细胞在肾小管间质纤维化大鼠肾脏中的定位与分布

肾小管间质纤维化（TIF）是几乎所有慢性肾脏疾病进展至终末期肾功能衰竭的主要原因之一，是临床治疗的难题。骨髓间充质干细胞（MSCs）是一类能够分化为多种骨髓间质成分的非造血多能干细胞，特定条件下可以分化为内胚层、脏壁中胚层和神经外胚层细胞。研究证实在急性肾脏损伤中MSCs可以被诱导分化成肾脏细胞，但在慢性肾小管间质纤维化中，移植的MSCs能否定位到损伤肾脏并分化为肾脏细胞、改善纤维化进程，还未检索到有关报道。本研究观察移植的MSCs在间质纤维化肾脏的定位分布及存活时间，为今后的研究提供理论依据。     

足细胞分子nephrin在高血压大鼠肾脏的表达及作用

目的探讨足细胞分子nephrin在自发性高血压大鼠（SHR）肾脏的表达及作用。方法监测不同时期SHR与京都大鼠（wistar-kyotorats,WKY）尾动脉收缩压（SBP）、尿β2-微球蛋白（β2-MG）、尿素氮（BUN）、血肌酐（SCr）水平;免疫组化、RT-PCR方法检测nephrin蛋白及mRNA的表达,观察肾脏的病理改变。结果与WKY组相比,SHR组SBP、β2-MG、BUN、SCr升高,nephrin蛋白及mRNA表达量下降,且nephrin含量与尿β2-MG呈负相关。SHR组肾脏发生病理改变。结论足细胞分子nephrin在SHR肾小球表达减少,可能是导致足细胞裂隙膜损伤,引起尿β2-MG排泄水平增加,肾功能受损,肾脏病理改变的基础。     

冬虫夏草通过诱导血色素加氧酶-1表达抑制肾小管间质纤维化

目的：观察冬虫夏草对单侧输尿管梗阻（unilateral ureteral obstruction,UUO）模型大鼠肾小管间质纤维化进展的保护作用。方法：72只雄性清洁级SD大鼠随机分为4组：假手术组,UUO模型组,UUO加冬虫夏草治疗组,UUO加冬虫夏草和血色素加氧酶抑制剂卟啉锌[（zinc（a）protoporphyrinη,znpp）]治疗组。各组大鼠分别于术后（建模后）第3、7、14天分批处死,留取手术侧（模型组梗阻侧）肾脏组织。采用HE、Masson染色、荧光定量PCR、免疫组织化学染色评价肾小管间质纤维化损伤程度并检测肾脏组织血色素加氧酶-1（hemoglobin oxygenase-1,HO-1）,α平滑肌肌动蛋白（α-smooth muscle ac-tin,α-SMA）mRNA及蛋白表达变化情况。结果：冬虫夏草治疗组相对于UUO模型组,肾脏病理损伤及进展程度明显减轻且HO-1的表达上调,α-SMA的表达下调（P〈0.05）,而冬虫夏草加HO-1抑制剂znpp后,以上作用明显减弱。结论：冬虫夏草可以通过诱导血色素加氧酶的表达减轻肾小管间质纤维化程度。     

大剂量螺内酯对自发性高血压大鼠肾脏纤维化的影响

目的 观察大剂量螺内酯对自发性高血压大鼠（SHR）肾脏纤维化的影响。 方法 8周龄的雄性SHR 24只随机分为低剂量和大剂量螺内酯干预组[分别为20和100 mg&#8226;kg-1&#8226;d-1螺内酯灌胃]和高血压对照组，同时设同源正常对照组京都大鼠（WKY）8只。干预8周，检测收缩压、尿蛋白、血白蛋白、钾、钠、Scr和肾组织及血浆醛固酮水平。肾组织切片分别行HE和Masson染色，以评价肾小球损伤及肾小球内胶原沉积情况。免疫组化SABC法检测肾组织TGF-β1和醛固酮受体蛋白表达。RT-PCR检测肾组织TGF-β1和醛固酮受体mRNA水平。 结果 与高血压组大鼠相比，低剂量螺内酯干预后，尿蛋白减少（P < 0.05），血白蛋白升高（P < 0.05），血浆和肾组织醛固酮水平降低，但差异无统计学意义；大剂量螺内酯干预后，血压没有显著改变，尿蛋白显著升高[（27.3±4.5）比（24.5±3.2） mg/d， P < 0.05]，血白蛋白显著减少[（20.2±4.2）比（22.7±3.5） g/L, P < 0.05]，血浆和肾组织醛固酮水平显著升高[肾组织（28.3±1.5）比（22.2±0.6） ng/g， P < 0.05]。与高血压组比较，低剂量螺内酯干预后，蛋白管型增多、管周炎性细胞浸润均减少（P < 0.05）；大剂量螺内酯干预后，蛋白管型、小管扩张加重，管周炎性细胞浸润明显增多（P < 0.05），肾小球内胶原形成亦明显增多（P < 0.05）。与高血压组大鼠比较，低剂量螺内酯干预后，肾组织醛固酮受体mRNA和蛋白表达均无显著改变，TGF-β1 mRNA和蛋白的表达显著减少（P < 0.05）；大剂量螺内酯干预后，肾组织醛固酮受体及TGF-β1 mRNA和蛋白的表达均显著升高(P < 0.05)。 结论 大剂量螺内酯可以加重高血压肾脏纤维化，可能是通过上调醛固酮及其受体表达实现的。     

甘草酸二胺对输尿管梗阻大鼠肾间质纤维化的治疗作用及机制

目的：探讨甘草酸二胺对肾间质纤维化的作用及其机制。方法：以Wistar大鼠单侧输尿管梗阻（UUO）为模型，在不同的时间点（7d、14d、28d）观察梗阻侧肾间质纤维化指数；致纤维化的转化生长因子β1（TGF-β1）的表达情况；肾皮质中与肾脏纤维化相关的Smurf2、Smad7信号蛋白等的mRNA及蛋白表达。结果：（1）随着梗阻时间的延长，肾间质纤维化程度逐渐加重，Smurf2基因和蛋白质明显上调，呈时间依赖性（P〈0．01）；Smad7蛋白呈时间依赖性下调（P〈0．01），Smad7基因在各个时间点无明显变化；TGF-β1基因在UUO后第7d达高峰，此后逐渐下降，但仍然高于假手术组（P〈0．01）。（2）甘草酸能改善UUO所致的肾间质纤维化程度（P〈0．01），下调肾脏组织TGF-β1基因的表达（尸〈0．01）；减少Smurf2基因和蛋白质的表达，同时上调TGF-β1信号传导中抑制性因子Smad7的表达（P〈0．01）。结论：甘草酸二胺能保护UUO所致的肾间质纤维化损伤。其可能的作用机制为减少Smurf2核酸和蛋白质的表达，增加抗纤维化作用的Smad7蛋白表达；减少TGF-β1表达，阻止TGF-β1信号传导，从而阻断肾间质的纤维化。     

雷米普利对单侧输尿管梗阻大鼠肾组织BMP-7表达的影响

目的 观察雷米普利对单侧输尿管梗阻（unilateral ureteral obstructionUU0）大鼠肾脏间质损伤及骨形态蛋白-7（bone morphogenetic protein-7 BMP-7）表达的影响。方法3（）只雄性SD大鼠随机分为假手术组（SHAM组），1周模型组（UUO-1组），2周模型组（UU0-2组），1周干预组（ACEF1组），2周干预组（ACEF2组）。各组大鼠于术后相应时间（除UUO-1组为术后1周，其余各组均为术后2周）取梗阻侧肾组织行Masson染色，按小管问质损害的特征进行半定量评分，用RT-PCR方法检测肾组织BMP-7mRNA水平。结果①SHAM组肾间质损伤指数较低，BMP-7高表达于肾组织。UUO-1组与sHAM组比较，肾间质损伤指数增加，BMP-7表达下降，UUO-2组与UUO-1组比较，肾间质损伤指数增加，BMP-7表达下降；②ACEI-2组较UUO-2组肾间质损伤指数下降，BMP-7表达增加；③UUO-1组已有少量间质纤维化，在此基础上ACEF1组比UUO-2组肾间质损伤指数下降，BMP-7表达增加。结论①在肾间质纤维化模型中，随着肾间质纤维化的进展，肾间质损伤指数逐渐增加，BMP-7表达逐渐下降；②雷米普利可部分维持肾间质纤维化过程中BMP-7的表达，从而延缓肾间质纤维化进展，对已发生纤维化的肾组织仍然有此作用。     

蛋白尿致肾小管间质纤维化的机制及防治

肾间质纤维化是各种不同病因的慢性肾脏病进展到终末期肾病（ESRD）的共同病变过程。动物实验和临床试验表明，各种肾脏疾病进行性肾功能恶化主要取决于肾间质损伤的严重程度。蛋白尿是肾小球疾病的共同临床表现，长期蛋白尿不仅引起肾小球硬化，而且可以直接导致肾小管间质损伤，后者与肾小球疾病进展的关系更为密切。我们的研究发现，在血压、肾功能均正常且其他各项临床指标相近的条件下，显著蛋白尿IgA肾病患者的肾小球及肾小管间质损害程度更为严重，蛋白尿可作为独立的致病因子，直接造成IgA肾病患者肾小管间质损害。因此，研究肾间质纤维化的分子机制，探索有效的防治措施，对延缓ESRD的进程意义重大。本文重点阐述蛋白尿致肾小管间质损伤的机制及防治现况。     

慢性肾小球肾炎患者肾脏BMP-7表达与肾间质纤维化程度的观察

目的观察慢性肾小球肾炎肾组织骨形态发生蛋白-7（BMP-7）、Ⅲ型胶原（Col-Ⅲ）、旷平滑肌肌动蛋白（α-SMA）的表达、肾间质纤维化程度及肾功能的关系和临床应用价值。方法采用免疫组化二步法（SP法）检测60例慢性肾小球肾炎及6例正常肾组织中BMP-7、Col-Ⅲ、α-SMA表达，并用计算机图像分析软件检测肾小管间质BMP-7、Col-Ⅲ、α-SMA阳性染色相对面积，同时检测慢性肾小球肾炎患者肌酐清除率、24小时尿蛋白、血清白蛋白、总蛋白改变；常规病理检查。结果①与正常对照组比较，慢性肾小球肾炎患者BMP-7表达明显下降（P〈0．01）；②BMP-7表达随着肾小管间质纤维化加重呈明显降低趋势，并同Col-Ⅲ、α-SMA的表达呈显著负相关。结论BMP-7表达与慢性肾小球肾炎肾间质纤维化程度密切相关，它可以作为慢性肾小球肾炎肾间质纤维化程度的标志。     

巨噬细胞移动抑制因子在原发性肾小球肾炎肾脏组织中的表达及其意义

目的 研究巨噬细胞移动抑制因子（MIF）在原发性肾小球肾炎患者肾脏组织中的表达水平及其与巨噬细胞浸润、肾脏病理改变、肾功能损害的相关关系。方法 正常人和原发性肾小球肾炎患者肾组织MIF蛋白、巨噬细胞标记抗原（抗CD68,KPI）的检测应用微波免疫组织化学染色方法检测;MIF的基因表达应用原位杂交方法;MIF与KP1的相关关系应用免疫组织化学双标记技术检测。肾脏组织的病理改变应用常规病理学方法检测。24h尿蛋白、血肌酐的测定按本院检验科常规方法检测。结果 正常人肾脏组织仅有少量MIF的表达,原发性肾小球肾炎患者肾脏组织MIF表达水平（包括蛋白和mRNA）显著上调。原发性肾小球肾炎患者肾组织MIF表达水平与KP1^ 细胞数有显著相关性,MIF表达水平、MIF^ KP1^ 细胞数与肾脏病理改变程度及肾功能损害明显相关。结论 MIF在原发性肾小球肾炎患者肾脏组织的表达水平显著上调;并与肾脏组织巨噬细胞浸润、肾脏病理改变程度、肾功能损害密切相关,提示MIF表达水平显著上调可能是原发性肾小球肾炎患者肾损害的重要机制之一。     

骨髓间质干细胞对大鼠急性肾小管损伤修复的促进作用

目的 观察骨髓间质干细胞(MSCs)对氯化汞(HgCl2)导致的急性肾小管损伤有无治疗作用，并探讨其可能的机制。 方法 建立HgCl2腹腔注射导致大鼠急性肾衰竭模型。SD大鼠分为MSCs组(HgCl2+MSCs)、生理盐水组(HgCl2+生理盐水)及正常对照组。7 d后，观察体重、生存率、肾功能、肾脏病理改变，进行增殖细胞核抗原(PCNA)、巨噬细胞标志物ED-1和增强绿色荧光融合蛋白(EGFP)免疫组织化学染色，用RT-PCR技术检测肾组织内细胞因子的表达情况，并观察EGFP转基因的MSCs在肾脏的分布情况。 结果 MSCs组在体重、生存率、肾功能、肾脏病理改变上，均明显好于生理盐水组；肾组织内PCNA+及ED-1+细胞数明显少于生理盐水组；促进肾小管损伤修复的生长因子表皮生长因子(EGF)、血小板源生长因子(PDGF)、肝细胞生长因子(HGF)在肾组织内表达明显高于生理盐水组，而促炎症因子TNF-α则明显低于生理盐水组。7 d时，间质干细胞在肾间质中偶尔可见到，而肾小管中未见。 结论 MSCs输注可促进HgCl2所致的急性肾小管损伤的修复，其作用机制可能是通过调节肾组织中细胞因子的分泌起作用，而非完全依靠转分化成肾小管上皮细胞。     

细胞间黏附分子-1在自发性高血压大鼠肾损害作用的研究

目的：研究细胞间黏附分子-1（ICAM-1）在自发性高血压大鼠（SHR）肾组织的表达及其与肾损害的关系。方法：以同龄雄性正常血压大鼠（WKY）和SHR为研究对象,分别于10周龄和28周龄检测两种大鼠尾动脉压、24h尿蛋白定量、肾功能等;留取肾组织行HE染色、免疫组织化学及RT-PCR法检测ICAM-1蛋白及mRNA表达情况,并作分析。结果：与同龄WKY大鼠比较,SHR尾动脉压和24h尿蛋白定量明显增高（P〈0.05和P〈0.05）;与12周龄SHR比较,28周龄SHR尾动脉压和24h尿蛋白定量明显增加（P〈0.05和P〈0.05）。SHR组肾组织ICAM-1蛋白及mRNA表达较同龄WKY增强（P〈0.05）,28周龄SHR较10周龄SHR表达增强（P〈0.05）,ICAM-1表达与24h尿蛋白定量呈正相关（P〈0.05）。结论：SHR出现蛋白尿时,肾组织ICAM-1表达增强,炎症参与了高血压肾损害的发生。     

骨髓间充质干细胞促进大鼠IgA肾病修复

目的 观察骨髓间充质干细胞（MSC）对大鼠IgA肾病有无修复作用，并探讨其可能的机制。 方法 SD大鼠随机分为MSC注射组、生理盐水（NS）组及健康对照组。前两组以牛血清白蛋白(BSA)+葡萄球菌肠毒素B（SEB）＋皮下注射四氯化碳（CCl4）的改良法建立IgA肾病模型。体外连续培养SD大鼠MSC并通过流式细胞仪和成骨成脂细胞诱导分化鉴定MSC，用5-溴脱氧尿嘧啶核苷（BrdU）体外标记培养的MSC。移植后1周及4周分别观察3组的体质量、尿蛋白量（24 h）、肾功能、肾脏病理变化、IgA荧光沉积变化；ELISA法检测尿中的MCP-1、TGF-β1量；RT-PCR法检测肾组织中MCP-1、TGF-β1 mRNA的表达情况；免疫组化观察细胞因子及BrdU标记的MSC在肾组织中的分布情况。 结果 移植后1周，MSC组尿蛋白量（24 h）（36.86±4.78） mg，Scr（53.50± 6.28） μmol/L；NS组尿蛋白量（24 h）(66.98±5.86) mg，Scr (82.50±8.36) μmol/L，两组差异有统计学意义（均P < 0.05）；同时，MSC组MCP-1、TGF-β1在尿中的含量及肾脏中表达均显著低于NS组（均P < 0.05）。移植后4周，MSC组体质量、肾脏病理变化、IgA荧光沉积与NS组差异有统计学意义；MCP-1、TGF-β1在尿中的含量及肾脏中的表达与健康对照组差异无统计学意义。随时间延长，BrdU标记的MSC在肾组织中分布却逐渐减少。 结论 MSC输注可促进大鼠IgA肾病的修复，其作用机制可能并不完全是依赖于MSC的直接分化，而是通过调节肾组织中细胞因子的分泌和（或）其他的功能进行修复。     

Protective effect of resveratrol on renal damage in spontaneously hypertensive rats and the related mechanisms

Objective To investigate the protective effect of resveratrol (RSV) on renal damage in spontaneously hypertensive rats (SHR) and the related mechanisms on interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). Methods Twelve male spontaneously hypertensive rats were randomly divided into two groups: model group (SHR, n＝6）and RSV group (RSV, n＝6). Six male Wistar-Kyoto rats served as control group (WKY, n＝6). RSV (20 mg·kg-1·d-1) or vehicle were gavaged for 20 weeks. Microalbuminuria and urinary β2-microglobulin were determined by urine collection from 8:00 to 16:00 at 20th week. Scr, BUN and the renal pathological changes were measured after 20 weeks. Immunohistochemistry staining of fibronectin, collagenⅠ, IL-6 and ICAM-1 were used to analysis the changes of renal fibrosis and inflammation. Real-time PCR and Western blotting were used to measure the expression of IL-6 and ICAM-1 in kidneys. Results Compared with the control group, SHR significantly increased the level of microalbuminuria, urinary β2-microglobulin (P＜0.05), but they were diminished in RSV group (P＜0.05). The expressions of fibronectin, collagenⅠ, IL-6 and ICAM-1 by immunohistochemistry staining were augmented in SHR group, and were significantly inhibited in RSV group. Compared with the control group, the expressions of renal IL-6, ICAM-1 mRNA and protein were significantly increased in SHR group (P＜0.05), and RSV treatment significantly inhibited the up-regulation (P＜0.05). Conclusions RSV treatment can attenuate microalbuminuria, urinary β2-microglobulin and renal fibrosis in SHR rats. This renal protective effect is associated with the inhibition of IL-6, ICAM-1 expression, which suggesting that inflammation may be a potential therapeutic target of hypertensive renal damage.     

Renal effects of rapamycin in the spontaneously hypertensive rat

The effects of rapamycin (RAPA), administered at therapeutic doses, were investigated in the spontaneously hypertensive rat (SHR). Additionally, the reversibility of RAPA's renal effects was investigated at a supratherapeutic dose. At doses that were active in preventing heart and kidney allograft rejection in the rat (0.01–0.08 mg/kg i.v.), RAPA had no effect on kidney function or rat body weight gain. At higher doses (0.8 mg/kg), RAPA produced significant changes in kidney function parameters and caused a loss in body weight. Histopathologic changes, including necrotizing vasculopathy and tubular atrophy, were noted at therapeutic doses. The effects of RAPA on kidney function were completely reversible after a 2-week washout period, though the histopathologic changes were still evident. These studies demonstrate that RAPA does not impair kidney function at therapeutic doses when administered for 2 weeks but does appear to accelerate the naturally occurring renal lesions of the SHR.     

Role of androgens in the renal production of 20-hydroxyeicosatetraenoic acid in spontaneously hypertensive rats

The role of androgens in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was determined in the kidney of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The renal production of 20-HETE and blood pressure were higher in males than in females at 9 weeks of age. The renal production of 20-HETE was significantly greater in male SHR than in male WKY, whereas it was significantly lower in female SHR than in female WKY. The differences in the renal production of 20-HETE were consistent with the cytochrome P-450 4A protein levels. Plasma free-testosterone levels in male SHR were twice as high as those in male WKY. Castration and treatment with the androgen receptor antagonist, flutamide, reduced blood pressure, the renal production of 20-HETE, and P-450 4A protein levels in both strains. The renal production of 20-HETE was significantly lower in castrated SHR than in castrated WKY. These results indicate that the renal production of 20-HETE and the expression of P-450 4A have gender and strain-differences, and high levels of plasma androgens induce the expression of P-450 4A and the production of 20-HETE in the kidney of male SHR. The androgen-induced production of 20-HETE may be associated with hypertension in male SHR.     

大鼠骨髓间充质干细胞移植治疗肾小管间质损伤的实验研究

目的:探讨骨髓间充质干细胞(MSCs)移植对大鼠单侧输尿管梗阻(UUO)后肾小管间质损伤的治疗效果。方法:密度梯度离心法和贴壁细胞培养法结合分离纯化MSCs。取成年雄性Wistar大鼠40只,随机分为移植组(组A,n=15)、对照组(组B,n=15)、假手术组(组C,n=10)。移植组和对照组分别结扎左侧输尿管,制作肾小管间质纤维化模型。移植组于结扎当日肾脏多点注射Brd U标记的含MSCs 1×10~6的DMEM培养基50μl,对照组注射等量DMEM培养基。假手术组开腹但不结扎输尿管。术后第14天处死各组大鼠,行HE染色,观察肾脏病理变化;免疫组化方法测定BrdU阳性细胞在肾脏的分布以及TGF-β_1,Ki-67的表达情况。结果:HE染色显示移植组与对照组肾脏间质损伤严重,两组相比无明显差异,假手术组正常。移植组肾实质内可见Brd U标记的MSCs,向周围组织分散,形态上与肾间质成纤维细胞类似,肾小管上皮细胞中未发现MSCs掺入。移植组较对照组TGF-β_1表达差异无统计学意义。移植组Ki-67表达较对照组有明显增强。结论:UUO大鼠骨髓间充质干细胞移植后,肾小管及间质细胞增生明显增高,提示骨髓间充质干细胞同种异体移植可能通过促进肾脏细胞的增生对肾间质损伤起到一定治疗作用。具体机制尚待进一步研究。     

Increased genetic susceptibility to renal damage in the stroke-prone spontaneously hypertensive rat

BACKGROUND: The spontaneously hypertensive rat (SHR) develops much less renal damage than the stroke-prone strain of SHR (SHRsp) after salt-supplementation, and it has been proposed that these strains differ in their genetic susceptibility to renal damage. However, radiotelemetric BP measurements have shown that salt-supplementation results in more severe and accelerated hypertension in the SHRsp. Therefore, it is unclear whether the differences in renal damage are due to differences in BP exposure or true differences in intrinsic (genetic) renal susceptibility to hypertensive damage. METHODS: Kidney cross transplantation was performed between the SHR and SHRsp strains in uninephrectomized recipients to allow an investigation of the susceptibility to renal damage in SHR and SHRsp kidneys maintained in the same host and exposed to the same BP profile and metabolic environment. Following transplantation, BP was radiotelemetrically monitored before and after an 8% NaCl diet given to accelerate hypertension and renal damage. Then the kidneys were removed and renal damage was assessed histologically. RESULTS: In the SHR recipients, the SHRsp donor kidneys exhibited more hypertensive damage than the contralateral native SHR kidneys, but histologic evidence of mild cellular immunologic rejection also was observed that could have facilitated the increased renal damage. However, even in SHRsp recipients, the native SHRsp kidneys exhibited twice the damage seen in the contralateral transplanted SHR kidneys. CONCLUSION: These data unequivocally demonstrate that the SHRsp kidneys are intrinsically more susceptible than the SHR kidneys to renal damage when exposed to exactly the same BP and metabolic environment.     

Effects of Intercellular Adhesion Molecule-1 on Renal Damage in Spontaneously Hypertensive Rats

Aims: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory process and immune response. The aim of the study was to investigate ICAM-1 expression in the kidneys of spontaneously hypertensive rats (SHRs) and the relationship between the level of ICAM-1 and renal damage. Methods: Male Wistar–Kyoto (WKY) rat and SHR models were employed. Blood pressure (BP) was recorded using tail cuff method. Twenty-four hour proteinuria and β₂-microglobulin (β₂-MG) were measured using biuret method and radioimmunity kits, respectively. Biochemical parameters were measured after the animals were killed. ICAM-1 expression in renal tissue was assessed using western blot and real-time polymerase chain reaction (PCR). Results: It was observed that BP, proteinuria, and urine β₂-MG were more increased in SHR groups than that in the same age WKY groups. In SHR groups, BP, proteinuria, and urine β₂-MG at the 56th week were significantly higher than that at the 28th week. ICAM-1 protein and mRNA expression in SHR renal tissues was significantly increased in SHR groups compared with the same age in WKY rats. ICAM-l expression was positively correlated with proteinuria and urine β₂-MG. Conclusion: This study demonstrated that the renal expression of ICAM-1 was increased in SHR with renal damage, and inflammation may be involved in the hypertensive renal damage.