坎地沙坦对单侧输尿管梗阻大鼠肾间质纤维化及肾脏骨桥蛋白表达的影响

目的 观察坎地沙坦(CAN)对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响,并观察骨桥蛋白(OPN)与肾间质纤维化的关系及CAN干预对肾脏OPN表达的影响,探讨其在纤维化中的作用机制.方法 (1)36只成年雄性SD大鼠随机分为3组,每组12只:假手术组(Sham)、UUO模型组(UUO)、坎地沙坦治疗组(CAN).UUO模型组和CAN组大鼠行左侧输尿管结扎术,Sham组只游离左侧输尿管但不结扎.CAN组于术前1 d开始用CAN治疗[10 mg/(kg·d)]灌胃.术后第7、14天分别处死大鼠,左侧肾脏组织行Masson染色,免疫组织化学方法检测肾组织中OPN的表达,逆转录-聚合酶链反应(RT-PCR)检测OPN mRNA表达水平.结果 Masson染色结果显示术后7 d和14 d UUO组大鼠肾纤维化阳性面积分别为15.2%和24.8%,CAN组为1O.1%和18.5%.CAN组与UUO组大鼠术后7 d和14 d大鼠肾纤维化阳性面积差异有统计学意义(P＜0.05).UUO模型大鼠OPN蛋白及mRNA水平均较Sham组明显升高(P＜0.01),CAN组OPN蛋白及mRNA水平较UUO组明显降低(P＜0.05),但较Sham组高(P＜0.01).结论 CAN能有效地延缓UUO大鼠肾间质纤维化的进展,其延缓肾间质纤维化作用可能与下调OPN蛋白和mRNA有关.     

梗阻性肾病大鼠肾组织periostin的表达及意义

目的 研究梗阻性肾病大鼠肾组织periostin表达的变化及其与肾间质纤维化的相关性.方法 18只SD雄性大鼠按随机数字法分成3组:假手术组、模型组和贝那普利组,每组6只.用单侧输尿管结扎法建立梗阻性肾病大鼠模型.RT-PCR检测各组大鼠肾组织periostin和转化生长因子(TGF) β1的mRNA表达;ELISA检测各组大鼠肾组织periostin、血管紧张素Ⅱ( AngⅡ)、TGF- β1的蛋白水平;HE及Masson染色观察肾间质变化;免疫组化检测肾组织Ⅰ型胶原蛋白.结果 与假手术组比较,模型组大鼠肾组织periostin、TGF-β1、AngⅡ蛋白表达显著升高(均P＜0.05).与模型组比较,贝那普利组上述蛋白表达显著降低,差异有统计学意义(均P＜0.05).与假手术组比较,模型组大鼠肾组织periostin和TGF- β1的mRNA表达显著上调,差异有统计学意义(均P＜0.05),而贝那普利组periostin和TGF- β1的mRNA表达则显著下调(均P＜0.05).肾组织periostin蛋白表达与AngⅡ、TGF-β1和Ⅰ型胶原的蛋白表达以及肾间质纤维化积分均呈正相关(r值分别为0.652、0.781、0.776和0.825,均P＜0.05).结论 梗阻性肾病大鼠肾组织periostin呈高表达,其可能参与了梗阻性肾病肾间质纤维化进程.     

梗阻性肾病大鼠肾小管间质进行性纤维化的监测

目的:探讨梗阻性肾病肾小管间质进行性纤维变性的发展过程。方法:建立大鼠单侧输尿管梗阻模型(UUO),采用免疫组化染色方法测其双侧肾形态学改变及胶原Ⅳ蛋白和α平滑肌肌动蛋白(α-SMA)的沉积;应用RT-PCR定性和半定量的方法测其金属蛋白酶组织抑制剂1(TIMP-1)mRNA、胶原ⅣmRNA的表达。结果:随着梗阻时间延长,梗阻侧肾脏肾小管间质变宽,肾小球无明显变化。梗阻肾内的胶原Ⅳ蛋白和α平滑肌肌动蛋白沉积增加,差异有统计学意义(P<0.05)。胶原ⅣmRNA、TIMP-1mRNA表达明显增加,差异有统计学意义(P<0.05);对侧肾脏各项指标变化差异无显著性。结论:该模型稳定可靠,能较好地体现梗阻性肾病中肾小管间质纤维化进行性发展过程。     

维甲酸抑制大鼠单侧输尿管梗阻模型肾间质纤维化

目的探讨维甲酸对大鼠单侧输尿管梗阻(UUO)模型肾间质纤维化的影响。方法建立大鼠UUO模型前2d治疗组和对照组分别每天给予10mg/kg全反式维甲酸或溶媒皮下注射。观察模型第3、7和12天肾小管损害百分比、肾间质纤维化程度、肾间质巨噬细胞数、肾间质α-平滑肌肌动蛋白(α-SMA)、胶原Ⅲ和单核细胞趋化蛋白-1(MCP-1)mRNA的表达。结果维甲酸显著减轻肾小管损害和肾间质纤维化(P<0.01)。治疗组肾间质巨噬细胞数和肾间质α-SMA表达显著低于对照组(P<0.01)。维甲酸显著抑制胶原Ⅲ和MCP-1mRNA表达(P<0.01)。结论维甲酸减少大鼠UUO模型肾间质巨噬细胞浸润、降低胶原Ⅲ和MCP-1mRNA表达、抑制α-SMA蛋白的表达,从而减轻肾间质纤维化。     

肾炎防衰液对延缓慢性肾脏病抗氧化应激机制研究

目的:研究肾炎防衰液对延缓慢性肾脏病抗氧化应激的疗效及作用机制。方法:采用UUO建立大鼠肾间质纤维化模型,随机分为模型组、贝那普利组和肾炎防衰液组,另设假手术组;术后7 d、14 d、21 d分批取材,检测肾脏羟脯氨酸含量及T-AOC、总T-SOD和MDA含量,免疫组化法检测肾组织MCP-1蛋白及TNF-α蛋白的表达,Real time PCR法检测肾脏NADPH氧化酶p22phox mRNA的表达。结果:与模型组相比,肾炎防衰液组UUO大鼠肾组织中T-AOC、总T-SOD和MDA含量均升高(P0.05),肾组织MCP-1蛋白、TNF-α蛋白及NADPH氧化酶p22phox mRNA的表达均减少(P0.05)。结论:肾炎防衰液可以升高T-AOC、总T-SOD和MDA水平,降低MCP-1蛋白、TNF-α蛋白及NADPH氧化酶p22phox mRNA的表达,减轻大鼠肾间质纤维化的程度,从而验证了肾络癥瘕理论在治疗慢性肾脏病中的作用。     

转化生长因子-β1 在梗阻性肾病大鼠肾小管间质纤维化中的作用

目的探讨转化生长因子 (TGF) -β1在梗阻性肾病(UUO)大鼠梗阻肾中致肾小管间质进行性纤维化的作用.方法成年SD大鼠制成UUO模型,在梗阻后3、7、10、14 d处死.免疫组织化学染色法对其肾内α-平滑肌肌动蛋白(SMA)沉积量及侵入肾内的单核巨噬细胞数进行分析;逆转录多聚酶链反应(RT-PCR)对大鼠TGF-β1 mRNA、金属蛋白酶组织抑制剂(TIMP)-1 mRNA及IV型胶原(Col-IV) mRNA转录量进行分析.结果随梗阻时间延长,侵入梗阻肾内单核巨噬细胞数、α-SMA沉积、Col-IV mRNA及TIMP-1 mRNA含量增加;示肾小管间质存在进行性纤维化.同时TGF-β1 mRNA含量明显增加,差异统计学意义(P<0.05).结论 TGF-β1促使梗阻性肾病大鼠肾小管间质进行性纤维化.     

怡肾丸对单侧输尿管结扎模型大鼠肾脏TGF-β1及P38MAPK表达的影响

目的:观察不同时相单侧输尿管结扎(UUO)模型大鼠肾脏组织,通过测定肾脏组织TGF-β1及丝裂原活化蛋白激酶p38(P38MAPK)的含量,探讨怡肾丸是否是通过阻断P38MAPK信号传导通路来延缓肾间质纤维化的发展从而达到保护肾脏的目的。方法:采用UUO诱导的肾间质纤维化模型,分别于造模后3、7、14d三个时间点处死该时间点大鼠,并用免疫组化法检测大鼠肾脏TGF-β1及P38MAPK的表达。结果:(1)怡肾丸组对改善大鼠活动等均优于其余各组;(2)通过采用HE及Masson染色观察UUO大鼠肾小管间质组织形态学的改变;(3)免疫组化结果提示怡肾丸组及依那普利组肾小管上皮细胞TGF-β1及P38MAPK的表达低于模型组。结论:(1)P38MAPK的活性在大鼠梗阻性肾病组织中随时间增加明显增高,提示P38MAPK的活化与肾间质纤维化有正相关。(2)怡肾丸可能通过抑制TGF-β1及P38MAPK的表达,减轻炎症反应和纤维化程度,从而达到保护肾脏、延缓肾间质纤维化的作用。     

MCP-1、ICAM-1在糖尿病肾病大鼠肾脏损害中作用及厄贝沙坦干预的影响

目的：探讨MCP-1、ICAM-1在糖尿病肾病大鼠肾脏损害中作用及厄贝沙坦对二者的影响.方法：采用高糖高脂饮食合并链脲佐菌素腹腔注射的方法建立糖尿病肾病大鼠模型.将大鼠随机分为正常对照NC 组、糖尿病肾病DN组、厄贝沙坦DI组,检测各组大鼠24 h尿量、24 h尿白蛋白定量（24 h UTP）、血糖（BG）、血肌酐（Scr）、尿素氮（BUN）、肾重指数（KI）;行HE染色观察各组大鼠病理学形态,免疫组化观察MCP-1、ICAM-1蛋白的表达,RT-PCR观察MCP-1 mRNA、ICAM-1mRNA的表达.结果：与NC组比较,DN组大鼠肾脏病理改变加重,24 h尿量、24 h UTP、KI、BG、Scr、BUN、肾脏组织中MCP-1mRNA和ICAM-1mRNA及蛋白水平均显著增加,差异均有统计学意义（P＆lt;0.01）;与DN组比较,DI组大鼠BG、BUN、Scr有所改善,差异无统计学意义;肾脏病理改变减轻,其余指标明显降低,差异有统计学意义（P＆lt;0.05）.结论：MCP-1、ICAM-1在糖尿病肾病肾脏损害过程中可能起重要作用;厄贝沙坦能够减轻糖尿病肾病肾组织MCP-1、ICAM-1的表达,缓解了肾脏病理损伤.     

安博维对环孢素A慢性肾毒性大鼠肾间质骨桥蛋白表达及巨噬细胞浸润的影响

目的①观察安博维(厄贝沙坦)干预治疗后环孢素A(CsA)所致慢性肾毒性大鼠肾脏病理变化。②观察安博维对CsA慢性肾毒性大鼠模型肾骨桥蛋白(OPN)表达及间质ED1阳性巨噬细胞浸润的影响,以探讨安博维防护CsA慢性肾毒性的可能机制。方法给进低盐饮食SD大鼠灌胃20mg·(kg·d)-1剂量的CsA制作大鼠CsA肾毒模型,同时以10mg·(kg·d)-1剂量的安博维胃饲以预防肾毒性。于用药后第1、2、4周末时分别处死各组大鼠,免疫组织化学法测定OPN、ED1的表达,用HE染色观察肾脏病理变化。结果安博维能明显改善CsA肾中毒大鼠的一般情况,减少肾小管上皮细胞空泡变性和萎缩,减少间质炎细胞浸润及间质纤维化。免疫组化结果显示模型组肾小管-间质OPN与ED1表达较对照组增加(p<0.05);在试验各时间点,安博维组大鼠肾小管-间质ED-1阳性巨噬细胞数量及OPN表达较模型组显著减少(p<0.05);OPN仍高于对照组((p<0.05),ED-1阳性巨噬细胞数量在第1、2周末与对照组无差异(p>0.05),但在第4周末高于对照组(p<0.05)。结论安博维能减轻CsA慢性肾毒性的肾脏病理损伤,这一防治作用可能与其减少ED-1阳性巨噬细胞浸润及下调OPN表达有关。     

HIF-VEGF-Notch信号通路相关因子在阿霉素肾病大鼠肾小球硬化过程中的表达研究

目的:探讨HIF-VEGF-Notch信号通路相关因子在阿霉素肾病大鼠肾小球硬化过程中的表达。方法:SD大鼠随机分为对照组和模型组(实验组),建立阿霉素肾病大鼠模型,第4、8、12、16周检测大鼠24 h尿蛋白、血清白蛋白(Alb)、尿素氮(BUN)、肌酐(Scr),光镜下观察肾组织病理改变,采用RT-PCR检测肾组织HIF-1 mRNA、VEGF mRNA、Notch1 mRNA表达水平,并采用Western blot法检测肾组织缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、Notch1蛋白表达水平。结果:实验组大鼠肾脏呈典型的肾小球硬化改变。与对照组相比,第4、8、12、16周实验组大鼠尿蛋白明显升高(P 0. 01); Alb均明显下降(P 0. 01); BUN、Scr持续升高,有显著性差异;实验组大鼠肾组织第4、8、12、16周HIF-1 mRNA、VEGF mRNA、Notch1 mRNA均表达升高(P 0. 01);肾组织HIF-1α、VEGF、Notch1蛋白水平也明显升高(P 0. 01)。结论:HIF-VEGF-Notch信号通路相关因子的高表达可能与阿霉素肾病肾小球硬化进展有关。     

Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to interstitial fibrosis. The molecular and cellular mechanism(s) of interstitial fibrosis in UUO kidney is beginning to be elucidated. Oxidative stress has been implicated in the pathogenesis of various forms of renal injury; however, little is known about its involvement in the setting of ureteral obstruction. METHODS: To investigate the possible involvement of oxidative stress in the obstructive nephropathy, we studied the occurrence and distribution of Nepsilon-carboxymethyl-lysine (CML) in the kidneys after ureteral obstruction. CML is an integrative biomarker of the cumulative protein damage induced by glycoxidation. Heme oxygenase-1 (HO-1) mRNA and protein expression, which is a sensitive and reliable indicator of oxidative stress, were also examined. RESULTS: CML immunoreactivity was found in the interstitium of UUO kidneys 10 days after the onset ureteral obstruction. HO-1 mRNA was up-regulated as early as 12 hours after ureteral obstruction. HO-1 immunoreactivity was observed in the periglomerular and peritubular interstitium two days after ureteral obstruction. CONCLUSIONS: These results strongly suggested the presence of increased oxidative stress in the interstitium of UUO kidneys. The oxidative stress and the formation of various kind of biological active oxidative products in the interstitium are supposed to play significant roles in UUO kidney.     

Altered expression of immune modulator and structural genes in neonatal unilateral ureteral obstruction

BACKGROUND: Congenital obstructive nephropathy is a condition characterized by hydronephrosis, tubular dilatation, apoptosis, and atrophy, as well as interstitial cellular infiltration and progressive interstitial fibrosis. The renal consequences of chronic unilateral ureteral obstruction (UUO) in the neonatal rat are similar to those of clinical congenital obstructive nephropathy. METHODS: To define alterations in renal gene expression induced by chronic neonatal UUO, Sprague-Dawley rats were subjected to UUO or sham operation within the first 2 days of life, and kidneys were harvested after 12 days. RESULTS: Microarray analysis revealed that the mRNA expression of multiple immune modulators, including krox24, interferon-gamma regulating factor-1 (IRF-1), monocyte chemoattractant protein-1 (MCP-1), interleukin-1beta (IL-1beta), CCAAT/enhancer binding protein (C/EBP), p21, c-fos, c-jun, and pJunB, was significantly increased in obstructed compared to sham-operated kidneys (all P < 0.05). Western blot analysis revealed significant changes in immune modulator protein abundance in the obstructed versus sham-operated kidney for krox24 (P = 0.0004), IRF-1 (P = 0.005), MCP-1 (P = 0.01), and JunD (P = 0.0008). Alternatively, the abundance of all of the immune modulator proteins was similar in sham-operated and obstructed kidneys in rats subjected to acute (4 days) neonatal UUO. Microarray analysis studies also reveal that structural genes that comprise the cytoskeleton and cell matrix are significantly up-regulated by chronic neonatal UUO, including calponin, desmin, dynamin, and lumican (all P < 0.05). CONCLUSION: Multiple genes are aberrantly expressed in the kidney of rats subjected to chronic neonatal UUO. Elucidation of these genes involved in neonatal UUO may lead to new insight about congenital obstructive nephropathy.     

mRNA expression of chemokines in rat kidneys with ureteral obstruction

BACKGROUNDS: It has been demonstrated that leukocyte infiltration, mainly of macrophages and lymphocytes, into obstructed kidneys (OBK) of rats during unilateral ureteral obstruction (UUO). Chemokines (C-C subfamily) may be involved in this mechanisms. Thus, we accessed the gene expression of chemokines in renal cortex of rats with UUO. MATERIALS AND METHODS: Female SD rats were sacrificed at various time points after UUO. mRNA expression of MCP-1, RANTES and MIP-1 alpha was determined by semi-quantitative RT-PCR. RESULTS: Control kidneys (CNK) showed a weak mRNA expression of MCP-1, RANTES and MIP-1 alpha. OBKs showed an increase in MCP-1 at 2 hours of UUO and a significant increase at 4 hours of UUO as compared with CNKs or contralateral unobstructed kidneys (CLK). The mRNA levels of RANTES and MIP-1 alpha were not increased until 72 hours of UUO in CLKs or OBKs. There were slight, but significant, differences of RANTES and MIP-1 alpha expression between OBKs and CNKs at 120 hours of UUO. CONCLUSIONS: We suggest that the early increase in MCP-1 contributes to the leukocyte infiltration and that RANTES and MIP-1 alpha plays a partial role in a late increases.     

N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸对肾间质纤维化大鼠MCP-1及NF-κB表达的影响

目的：观察N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）对单侧输尿管梗阻（UUO）所致大鼠肾间质纤维化的的保护作用并初探其机制。方法：雄性Wistar大鼠18只,随机分为假手术组、UUO组、治疗组（AcSDKP＋UUO）,每组各6只。于造模第14天处死大鼠,取其梗阻侧肾脏组织行HE、Masson染色,光镜下观察肾组织病理改变,评价肾小管变性程度及肾间质纤维化指数,免疫组织化学检测各组肾脏组织MCP-1、ED-1及NF-κB蛋白表达,RT-PCR检测MCP-1 mRNA的表达,Western blot检测NF-κB的蛋白质表达。结果：与假手术组相比,UUO组大鼠肾脏肾小管变性及肾间质纤维化程度严重,AcSDKP治疗后可明显改善UUO组大鼠肾小管变性和间质纤维化（P〈0.05）;免疫组化染色显示：MCP-1、ED-1及NF-κB的蛋白表达UUO组和治疗组明显多于假手术组,但治疗组较UUO组明显减少（P〈0.05）;AcSDKP治疗组MCP-1 mRNA及NF-κB蛋白质的表达均显著弱于UUO组,二者相比差异有统计学意义（P〈0.05）。结论：AcSDKP通过抑制NF-κB激活并进一步减少下游炎症细胞因子的表达以达到治疗肾间质纤维化的作用。     

Urinary concentration and tissue messenger RNA expression of monocyte chemoattractant protein-1 as an indicator of the degree of hydronephrotic atrophy in partial ureteral obstruction

PURPOSE: To find a potential prognostic marker of the induction of hydronephrotic atrophy in congenital hydronephrosis we investigated whether the messenger (m)RNA expression and urinary concentration of monocyte chemoattractant protein-1 (MCP-1) correlated with the degree of partial ureteral obstruction, and subsequent hydronephrotic atrophy and interstitial fibrosis. MATERIALS AND METHODS: We created left partial ureteral obstruction in 96 juvenile Wistar rats and complete ureteral obstruction in 18, while 16 underwent sham operation. Depending on excretion of contrast medium into the renal pelvis after 3 days we defined 2 degrees of hydronephrosis. Renal mRNA expression of MCP-1, and renal pelvic and bladder urinary concentrations of MCP-1 were measured after 1, 2 and 3 weeks, and compared with the degree of hydronephrotic atrophy. RESULTS: Grade 1 partial ureteral obstruction resulted in mild histological changes. Grade 2 partial and complete obstruction resulted in significant hydronephrotic atrophy. MCP-1 mRNA expression in the kidney remained unchanged in grade 1 partial obstruction but was moderately increased in grade 2 partial obstruction and clearly over expressed in complete ureteral obstruction. The renal pelvic urinary concentration of MCP-1 was not higher in rats with grade 1 partial obstruction than in sham operated animals but it was significantly increased in those with grade 2 partial and complete obstruction. CONCLUSIONS: mRNA expression and the urinary concentration of MCP-1 correlate with the degree of obstruction and subsequent renal damage in hydronephrosis. They may serve as prognostic markers in children with congenital hydronephrosis.     

反义寡核苷酸对间质性肾炎肾小管上皮细胞骨调素表达的调节

目的 探讨骨调素（ＯＰＮ）反义寡核苷酸对间质性肾炎肾小管上皮细胞ＯＰＮ表达的影响。方法 以一侧输尿管梗阻（ＵＵＯ）所致的间质性肾炎为研究模型,肾动脉内注射全硫代修饰的ＯＰＮ反义寡核苷酸,免疫组织化学双染及原位杂交技术检测ＯＰＮ的表达及巨噬细胞的浸润。结果 ＯＰＮ及其ｍＲＮＡ在间质性肾炎的发展过程中表达明显升高,巨噬细胞的局部浸泣均发生在过度表达ＯＰＮ的肾小管周围;ＯＰＮ反义寡核苷酸能显著抑制肾小管     

The expression of mRNA for tumour necrosis factor-α increases in the obstructed kidney of rats soon after unilateral ureteral ligation

Summary: Cytokines, including transforming growth factor (TGF)-β1, contribute to the tubulointerstitial fibrosis of ureteral obstruction. Tumour necrosis factor (TNF)-α, a proinflammatory cytokine produced by multiple cells including macrophages and resident renal cells, has a role in inflammatory cell recruitment in glomerular injury. We measured TNF-α mRNA in the renal cortex of rats at different times after the onset of unilateral ureteral obstruction (UUO) and determined whether angiotensin II (AngII) inhibition or total body irradiation affects the mRNA levels of TNF-α. Rats were killed at 1, 2, 4, 24, 72 and 120h after UUO. Levels of TNF-α mRNA increased significantly in the obstructed kidney at 1h (X 2), 2h (X 2.7), 4h (X 3.6), 24h (X 2.7), 72h (X 1.8) and 120h (X 2.8) after ureteral ligation when compared to the contralateral kidney of the same animals or to control (normal) kidneys. Tumour necrosis factor-α mRNA increased in renal cortical tubules but not in glomeruli. Treatment with enalapril, an angiotensin-converting enzyme (ACE) inhibitor, before and after UUO decreased TNF-α mRNA levels in the obstructed kidney by about 40% at 4h after the onset of UUO, but at 120h there was no difference in TNF-α levels in the obstructed kidney of treated and untreated animals. Total body irradiation, which depletes macrophages in the obstructed kidney, did not prevent the upregulation of TNF-α mRNA expression at 4 h after UUO. Thus, TNF-α may have a role in initiating tubulointerstitial injury in the obstructed kidney. Leucocytes infiltrating the renal interstitium of the obstructed kidney do not appear to contribute to the increased mRNA expression of TNF-α. Angiotensin II may contribute, at least in part, to the early increased expression of TNF-α mRNA in the obstructed kidney.     

雌激素对单侧输尿管梗阻大鼠肾间质纤维化的保护作用

目的探讨雌激素对单侧输尿管梗阻（UUO）大鼠肾间质纤维化的作用。方法雌性SD大鼠30只，随机分为4组：Ⅰ组对照组；Ⅱ组生理雌激素组；Ⅲ组低雌激素组；Ⅳ组高雌激素组。UUO术后21d处死各组大鼠，光镜观察梗阻肾组织病理变化，并分别用免疫组化和RT-PCR方法检测各组肾组织α-平滑肌肌动蛋白（α-SMA）和金属蛋白酶1组织抑制剂（TIMP-1）的表达。结果低雌激素组间质纤维化病变最明显，高雌激素组病变显著减轻（P〈0．01）。与生理雌激素组相比，低雌激素组α—SMA和TIMP-1蛋白和基因的表达增加（P〈0．05）；高雌激素组上述物质表达则减少（P〈0．05）。结论雌激素可能通过抑制α-SMA和TIMP-1的表达进而减少细胞外基质的沉积而发挥肾保护作用。     

肝细胞生长因子负性调控细胞转分化在肾间质纤维化中的作用

目的 研究肝细胞生长因子(HGF)对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的保护作用及其可能机制&#65377;方法 大鼠随机分为UUO组&#65380;HGF治疗组和假手术组&#65377;用实时荧光定量RT-PCR&#65380;Western杂交和免疫组化检测术后大鼠肾组织结缔组织生长因子(CTGF)和骨形成蛋白7(BMP7)表达量&#65377;免疫组化检测大鼠肾组织TGF-β1&#65380;FN及α-SMA表达&#65377;结果 与假手术组相比,UUO组及HGF治疗组CTGF mRNA&#65380;TGF-β1&#65380;α-SMA&#65380;FN&#65380;CTGF蛋白表达均增高,且UUO组明显高于治疗组;UUO组及HGF治疗组BMP7 mRNA和蛋白表达均减少,且UUO组显著低于治疗组&#65377;结论 HGF能减轻肾间质纤维化,负性调控肾小管上皮细胞-肌成纤维细胞转分化,调节CTGF及BMP7表达可能是其作用途径&#65377;