银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

Objective To study the effect of ginkgo biloba extract (GbE) on the expression of matrix metalloproteinase (MMP)-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups: diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group ( P ＜0.05 ). The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats ( P ＜ 0.05 ) but showed no changes in GbE treatment group compared to diabetes group( P ＞ 0.05 ). The expression level of type Ⅳ collagen was significantly increased in diabetic rats( P ＜0.05 ) but showed no changes in GbE group( P ＞0.05). Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.     

银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

Objective To study the effect of ginkgo biloba extract (GbE) on the expression of matrix metalloproteinase (MMP)-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups: diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group ( P ＜0.05 ). The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats ( P ＜ 0.05 ) but showed no changes in GbE treatment group compared to diabetes group( P ＞ 0.05 ). The expression level of type Ⅳ collagen was significantly increased in diabetic rats( P ＜0.05 ) but showed no changes in GbE group( P ＞0.05). Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.     

肿瘤坏死因子α与白细胞介素6在糖尿病大鼠骨骼肌中表达的实验研究

目的 探讨糖尿病大鼠骨骼肌中炎性细胞因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6的表达及其与细胞凋亡的关系.方法 将Wistar大鼠16只分为实验组和对照组各8只.实验组饲以8周高脂高糖饮食后腹腔内注射小剂量链脲佐菌素(30 mg/kg).对照组仅注射柠檬酸-柠檬酸钠缓冲液.第13周末处死大鼠.观察TNF-α及IL-6的蛋白表达,检测骨骼肌细胞中caspase 3的表达,并计算二者的相关性.结果 与对照组数据[TND-a、IL-6、caspase 3分别为(0.63±0.35)%、(2.05±0.83)%、(10.02±0.82)%]相比,实验组大鼠骨骼肌中TNF-α与IL-6(3.75±1.38%,5.77±0.74%)的表达水平均升高(P＜0.01),caspase 3[(10.02±0.82)%]表达明显高于(P＜0.01),TNF-α、IL-6与caspase3的表达具有相关性(r=0.713,r=0.692,P＜0.05).结论 糖尿病骨骼肌病变时炎症与凋亡同时发生,并可能共同导致胰岛素抵抗.

Abstract：

Objective To evaluate changes of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)expression in quadriceps femoris muscle of diabetic and control rats, and to explore the corelation among TNF-α, IL-6 and caspase 3. Methods Totally 16 adult (aged 8 weeks) Wistar rats were divided into non-diahetic (n =8)group and diabetic (n = 8) group. Diabetic rats were fed by high lipid and glucose diet. After 8 weeks, they were made by a single injection of streptozotocin (STZ) at a dose of 30 mg/kg and control rats were injected by citrate buffer ( pH 4.5 ) in the same dose. Quantitative immunohistochemistry assay for TNF-α, IL-6 and caspase 3 was applied. The quantitative analysis was used to evaluate the positive rate of TNF-α, IL-6 and caspase 3 expression and correlation analysis was used to evaluate the corelation of them. Results TNF-α, IL-6 protein had higher expression (3.75 ± 1.38,5.77 ± 0.74) in quadriceps femoris muscle of diabetic rats than those in controls (P ＜ 0.01 ).Caspase 3 ( 10.02 ±0.82) had higher expression in muscle of diabetic rats than that in controls (P ＜0.01 ). There was significant correlation among TNF-α, IL-6 and caspase 3 (r=0. 713,r=0. 692,P ＜0.05). Conclusions In muscle of diabetic rats, apoptosis is closely related to TNF-α and IL-6 protein which may induce the insulin resistance.     

自发性2型糖尿病大鼠肺组织α平滑肌肌动蛋白表达的变化及罗格列酮对其影响

目的 探讨自发性2型糖尿病(OLETF)大鼠肺组织α-平滑肌肌动蛋白(α-SMA)表达的变化及罗格列酮对其影响.方法 30周龄雄性OLETF大鼠16只,分为OLETF组和OLETF/L组每组8只,对照组为8只LETO组大鼠.OLETF/L组大鼠给予罗格列酮3 mg/(kg·d)灌胃12周后处死大白鼠,应用免疫组织化学和免疫蛋白印迹法检测各组大鼠肺组织α-SMA蛋白表达.结果 各组大鼠肺组织α-SMA主要表达于肌成纤维细胞、血管平滑肌细胞、小气道平滑肌,OLETF组大鼠肺组织α-SMA蛋白表达(2.03±0.64)明显高于LETO组(1.18±0.35),P<0.05];OLETF/L组明显减少(1.34±0.40),差异均有统计学意义(均P<0.05).结论 OLETF大鼠肺组织肌成纤维细胞生成增多,罗格列酮可抑制成纤维细胞向肌成纤维细胞的转化,早期改善糖尿病肺纤维化.

Abstract：

Objective To investigate the changes of expression of α—smooth muscle actin(α-SMA)in lung of spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty(OLETF)rats and the effect by tlle rosiglitazone.Methods Totally 16 male OLETF rats in 30 weeks old were divided into OLETF group and OLETF／L group.The Long Evans Tokushima Otsuka(LETO)rats were in control group.Thle OLtErI’F.rats were given gastric lavage bymsiglitazone 3 ms／(kg·d)then were killed after 12 weeks.The levels of ct-SMA in lung of three groups were detected by immunohistochemistry and western blotting.Results α-SMA in lung of three groups mainly expressed in myofibmblast.vascular smooth muscle cells and small airway smootII muscle.Compared to control group,tlle levels of α-SMA in lung of OIJETF group were increased obviously(2.03-4-0.64 VS 1.18 4-0.35,P<0.05).Compared to OLETF group,the levels of α-SMA in lung of OLETF／L group were decreased obviously(1.34 ±0.40 VS 2.03 ±0.64.P<0.05).Conclusion Myofibroblast increases in lung of OLETF rats.Rosiglitazone can inhibit the transformation from fibroblast to myofibroblast and improve pulmonary fibrosis in diabetes in early stage.     

他克莫司与西罗莫司根据细胞周期序贯用药对阿霉素肾病大鼠的影响

目的 观察他克莫司、西罗莫司根据细胞周期序贯联合用药对阿霉素肾病大鼠的治疗效果.方法 将24只雄性SD大鼠模型完全随即分为正常对照组、肾病组及治疗组,各8只;测定3组大鼠的尿蛋白定量、血生化指标;免疫组化、定时定量聚合酶链反应检测肾组织Nephrin、Podocin表达以及肾组织结缔组织生长因子(CTGF)的表达.结果 ①肾病组在12周末可见肾小球出现局灶节段性硬化,治疗组病理变化明显减轻.②肾病组4、8、12周末尿蛋白定量[分别为(276.41±11.12)、(355.76±14.10)、(338.92 ±15.87)mg]均明显高于对照组[分别为(12.18±1.38)、(12.98 ±2.07)、(13.56±2.70)mg,P<0.01)],治疗组大鼠尿蛋白定量在8、12周末[分别为(160.64±13.72)、(126.30±14.65)mg]均明显低于肾病组(P<0.05),但高于对照组;肾病组TP、ALB明显低于对照组(P<0.01),肾病组TG、胆固醇明显高于对照组(P<0.01),治疗组TP、ALB明显高于肾病组(P<0.05).③在12周末肾病组大鼠Nephrin、Podocin蛋白和mRNA表达明显减少(P<0.01),治疗组表达较肾病组上调(P<0.05).④在12周末肾病组CTGF蛋白表达较对照组明显增加(P<0.01),治疗组较肾病组明显减少(P<0.05).结论 他克莫司、西罗莫司根据细胞周期序贯联合用药对阿霉素肾病大鼠肾组织病理学变化均有明显改善,可有效减少阿霉素肾病大鼠的尿蛋白;升高TP和ALB,降低TG和胆固醇;并可恢复足细胞相关蛋白的表达,改善肾脏纤维化.

Abstract：

Objective To assess the therapeutic effects of the sequential thempy regimens according to the theory of cell cycle in adriamycin-induced nephrooathy(AIN)rats.Methods AIN model rats were randomly divided into three groups:control group(n=8),AIN model group(n=8)and treated group(n=8).The level of24hour urinary protein,serum total protein(TP),albumin(ALB),cholesterin(Chol),triglyeride(TG),serum urea nitrogen(BUN),serum creatinine(Scr)were measured.The expression of Nephrin and Podocin were analyzed by 11.12),(355.76±14.10)and(338.92±15.87)mg]were obviously higher than control group[respectively (12.18±1.38),(12.98±2.07)and(13.56±2.70)mg].The level of24 hour urinary protein in model group at 8th and 12 th week[respectively(160.64±13.72)and(126.30±14.65)mg]was obviously lower than model group(P<0.05).The levels of TP and ALB in treatment group were significantly higher in AIN model group,and westemblot indicated the expression of CTGF in treatment group was higher than that in AIN model group(P<0.05).Conclusions The sequential combined regimens can improve the pathological changes in Adriamycin-in-duced nephropathy rats,decrease the excretion of urinary protein,increase the levels of TP and ALB and decrease the levels of TG and Chol.It also can increase the expression of Nephrin and Podocin,and ameliorate kidney fibrosis.     

Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU·kg-1·month-1 and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 mg·kg-1·d-1 was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang II-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P<0.05; MMP-9, 10527±1002 vs 14623±2462, P<0.01). In     

胶原关节炎大鼠滑膜组织核转录因子κB与白细胞介素1β和基质金属蛋白酶9相关性分析

目的 探讨白细胞介素1β(IL-1β)、基质金属蛋白酶9(MMP-9)、核因子κB(NF-κB)与类风湿关节炎发生发展的相关性.方法 构建Ⅱ型胶原诱导的胶原关节炎大鼠模型,分不同时点处死动物,检测滑膜细胞中IL-1β,NF-κB和MMP-9的表达,分析大鼠关节炎评分与滑膜细胞NF-κB、IL-1β、MMP-9的表达的相关性.结果 实验组造模前关节体积为(2.18±0.16)ml,造模后2、4、6周分别为(4.68±0.49)、(5.62±0.59)、(5.44±0.66)ml,与造模前比较,差异均有统计学意义(P＜0.01);对照组造模前和造模后2、4、6周关节体积分别为(2.15±0.26)、(2.38±0.32)、(2.19±0.31)、(2.18±0.26)ml.造模后2、4、6周实验组大鼠关节体积与对照组比较,差异有统计学意义(P＜0.01).实验组大鼠造模后2、4、6周关节指数分别为(8.00±0.32)、(9.80±0.66)、(9.40±0.51),与对照组(均为0)比较,差异有统计学意义(P＜0.05).大鼠关节指数与NF-κBp65呈显著正相关(r=0.593,P＜0.05);MMP-9与NF-κBp65呈显著负相关(r=-0.506,P＜0.05).结论 实验组大鼠滑膜组织中NF-κB与IL-1β表达水平显著高于正常对照滑膜组织,且与关节炎的评分有一定相关性;提示NF-κB在类风湿关节炎发病机制中起关键的调控作用.

Abstract：

Objective To investigate the corelation among interleukins-1β (IL-1β), matrix metalloproteinase 9 ( MMP-9), nuclear factor kappa B (NF-κB) and arthritis index (AI) in the development of arthritis, and to understand the pathology of synoviocyte. Methods Thirty-six female Wistar rats were randomly divided into two groups,namely the model controlled group and the normal controlled group; three subgroups were randomly divided into model group and controlled group. The model group rats were immunized with emuusified bovine type Ⅱ collagen in complete Freund'adjuvant by introdemal injection to induce collagen induced arthritis (CIA) on day1, day14 and day 28, while the controlled group were injected with saline at the same time. The model and the controlrats were killed at different times. We detected the expression and activation levels of IL-1β, MMP-9 and NF-κB in synovial tissue by immunohistochemistry. Then we analyzed the corelation between AI and the expression of IL-1 β, MMP-9 and NF-κB in the synovium and IL-6 and TNF-α in the serum. Results The joint volume of model group was (2. 18 ± 0. 16), (4.68 ± 0.49 ), (5.62 ± 0. 59), (5.44 ± 0.66 ) respectively before, 2, 4 and 6 weeks after setting up models. There were statistically significant differences between before and after setting up models ( P ＜ 0. 01 ).The joint volume of control group was ( 2. 15 ± 0.26), (2.38 ± 0.32), (2. 19 ± 0. 31 ), ( 2.18 ± 0.26 ) respectively before, 2, 4 and 6 weeks after making model. Through measuring joints sizes after successfully modeling 2, 4 and 6 weeks, there were statistically significant differences between model and control group( P ＜0.01 ). MMP-9 showed significant negative correlation with NF-κB P 65 ( r = -0. 506, P ＜ 0.05 ). Conclusions The expression levels of IL-1 β and NF-κB are significantly higher in CIA synovial than those in control group and show a positive correlation with AI. NF-κB plays acritical role in the pathology of RA via regulating inflammation reaction, facililating the prolifteration of synoviocyte and participating the reestablishment of articulation.     

长春西汀对慢性阻塞性肺疾病大鼠炎症干预作用的探讨

目的 探讨长春西汀对慢性阻塞性肺疾病(COPD)慢性炎症的作用.方法 将40只雄性Wistar大鼠随机分为正常对照组、COPD模型组、长春西汀5 mg/kg组、2.5 mg/ks组和1.25 mg/ks组,每组8只.采用熏香烟加气管内注入脂多糖法建立COPD大鼠模型.长春西汀组(共3组)从注入脂多糖次日起给予长春西汀腹腔注射,每日1次.观察各组大鼠肺组织病理改变,检测血清中肿瘤坏死因子(TNr)-a、白细胞介素(IL)-8、C反应蛋白(CRP)的浓度以及支气管肺泡灌洗液(BALF)中TNF-a、IL-8的浓度.结果 COPD模型组肺组织病理改变符合人类COPD的病理特点;长春西汀5 mg/kg组和2.5 mg/kg组病理改变较模型组轻;上述两组血清IL-8浓度分别为(18.40±2.40)和(19.30±3.11)ng/L,比COPD模型组[(23.81±3.54)ns/L]低,血清TNF-a浓度分别为(39.34±3.43)和(40.47±3.09)ns/L,比COPD模型组[(46.65±4.42)ns/L低],血清CRP浓度分别为(4.28±0.22)和(4.35±O.26)ms/L,比COPD模型组[(4.69±0.19)ms/L]低;上述2组肺泡灌洗液中IL-8浓度分别为(20.09 ±2.88)和(21.03±2.21)ng/L,低于COPD模型组[(25.02±2.92)ng/L],TNF-a浓度分别为(40.41±4.40)和(41.18±5.33)ng/L,低于COPD模型组[(48.81±4.92)ng/L],差异均有统计学意义.长春西汀1.25 mg/ks组各项指标与COPD模型组比较,差异无统计学意义(P>0.05).结论 长春西汀能降低COPD大鼠血清和BALF中炎性因子的水平,减轻气道及肺组织炎症,对COPD大鼠的炎症反应有一定的抑制作用.

Abstract：

Objective To observe the effect of vinpecetine on inflammatory factors and lung pathology of the rats with chronic obstructive pulmonary disease(COPD),and to investigate the therapeutic action of vinpecetine on COPD.Methods Totally 40 Wistar rats were randomly divided into the normal control group,the COPD model group and three viupocetine treated groups.The COPD rat model wag established by intratracheal instillation of lipepalysaceharide and exposure to cigarette smoke.The three intervention groups were intrapedtonealy injected with vinpecetine respectively at the dose of 1.25 mg/kg,2.5 mg/kg and 5 mg/kg before exposing to cigarette smoke.Pathologic changes of the lung tissue,interlukin(IL)-8 and tumor necrosis factor (TNF)-a levels in bronchial alveolarhvage fluid(BALF)and seruln,and CRP level in the serum were determined.Results The pathological changes in the COPD rat model were coincident with the changes in human.Compared with the COPD model group,the two groups treated with vinpecetine at the dose of 2.5 mg/kg and 5 mg/kg showed a significan t decrease in IL-8[(18.40 ±2.40)ng/L,(19.30±3.11)ng/L respectively vs(23.81±3.54)ng/L],TNF-a[(39.34±3.43)ng/L,(40.47±3.09)ns/L respectivelyvs (46.65±4.42)ng/L],and CRP[(4.28±0.22)mg/L,(4.35±0.26)mg/L respectively vs(4.69±0.19)mg/L]in serum.In the BALF of those the BALF of those two groups, the levers of Ⅱ-8[(20.09 4±2.88)ng/L,(21.03±2.21)ng/L]and TNF-a[(40.41±4.40)ng/L,(41.18 4±5.33)ng/L]were also significantly lower than those in the moder group[(25.02±2.92).g/L,(48.81±4.92)ng/L].The vinpocetine treated group at the dose of 1.25mg/kg ad no significant difference, compared with the COPD model group. Conclusions Vinpocetine can reduce the levels of inflammatory factors in BALF and the serum of the rats with COPD and decrease inflammation of the airway and lung tissue. Accordingly vinpecetine can inhibit the inflammation of the COPD rat model.     

2型糖尿病视网膜病变患者血清D-二聚体与肿瘤坏死因子α和白细胞介素6的检测价值

目的 研究2型糖尿病视网膜病变(DR)患者血清D-二聚体(D-D)、肿瘤坏死因子α(TNF-α和白细胞介素-6(IL-6)水平检测的临床价值.方法 通过眼底血管荧光造影和眼底检查,将80例糖尿病患者分为糖尿病视网膜病变(DR)组(42例)和糖尿病无视网膜病变(NDR)组(38例),另选健康体检者30例作为对照(对照组),对3组D-D、TNF-α和IL-6进行检测.结果 对照组、NDR组及DR组的D-D、TNF-α、IL-6水平分别为(0.34±0.12)mg/L、(4.5±1.7)ng/L、(66.5±19.3)ng/L;(0.59±0.19)mg/L、(15.5±7.9)ng/L、(101.18±30.1)ng/L;(1.08±0.27)ms/L、(42.1±12.6)ng/L、(161.2±48.8)ng/L.糖尿病患者血清D-D、TNF-α和IL-6水平均明显高于对照组(均P<0.05),DR组血清D-D、TNF.仅和IL-6水平均高于NDR组(均P<0.05).结论 DR患者D-D、TNF-α和IL-6水平明显升高,提示此类患者处于高凝状态,且炎症反应可能在糖尿病视网膜DR发展中起重要作用.

Abstract：

Objective To investigate the clinical value of D-dimer (D-D),tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels in type 2 diabetic patients with diabetic retinopathy. Methods All the patients had routine FFA and examination of fundus and were divided into two groups based on the results: normal fundus( NDR group n = 38 ) , diabetic retinopathy( DR group n = 42 ). Thirty healthy subjects were used as control group. The serum levels of D-D, IL-6 and TNF-a was detected. Results The serum levels of D-D, IL-6 and TNF-a of type 2 diabetic patients were higher than those of control group statistically (P < 0.05). The serum levels of D-D, IL-6 and TNF-a of DR group were higher than those of NDR group(P <0.05). Conclusions The levels of D-D, IL-6 and TNF-a in type 2 diabetic patients with diabetic retinopathy are higher than those of normal fundus group. The inflammatory reaction may play an important role in the initiation and sustainment of DR.     

Therapeutic effect of Turkish galls extract on iga nephropathy model rats北大核心CSCD

OBJECTIVE: To investigate the effect of Turkish galls extract (TGE) on the expression of IgA in serum, urine and renal tissue of IgA nephropathy (IgAN) model rats. METHODS: Fifty healthy male Sprague Dawley rats were randomly divided into normal control group, IgAN model group, and TGE 75,150 and 300 mg · kg-1 groups, 10 rats per group. The model of IgAN rats was established with bovine serum albumin (BSA) + lipopolysaccharide (LPS)+carbon tetrachlorid (CCI4)for 12 weeks. From the 13th week, TGE was ig administrated once a day for 4 weeks. At the end of the 12th and 16th weeks, 24 h urine protein was measured by BCA method. At the end of the 16th week, serum and urinary IgA levels were measured by enzyme linked immunosorbent assay(ELISA), serum creatinine(SCR) and blood urea nitrogen (BUN) were detected by an automatic biochemical analyzer, and the renal pathological changes were evaluated with an Oxford classification scoring system. The deposition of IgA immune complex in the kidney was observed by immunofluorescence assay. RESULTS: At the end of 12th week, 24 h urine protein increased in all IgAN groups (P<0.05), compared with normal control group. At the end of 16th week, 24 h urine protein, IgA content in serum and urine,SCr and BUN content in serum, score in Oxford classification of renal tissue and deposition of IgA immune complex in the kidney in IgAN model group were all higher than in normal control group (P<0.05). Compared with IgAN model group, 24 h urine protein, IgA content in serum and urine and SCr content in serum were decreased in all TGE groups (P<0.05), and BUN content in serum and deposition of IgA immune complex in the kidney decreased in TGE 150 and 300 mg · kg-1 groups (P<0.05). The score in Oxford classification of renal tissue was decreased in TGE 300 mg.kg-1 group only. CONCLUSION: TGE has curative effect on IgAN model rats by reducing serum and urinary IgA and decreasing IgA immune complex deposition.     

厄贝沙坦对糖尿病大鼠肾组织MMP-2、TIMP-2和Ⅳ-C表达的影响

目的:观察基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)和Ⅳ型胶原(Ⅳ-C)在糖尿病大鼠肾组织中的表达及厄贝沙坦干预后的影响。方法:30只♂SD大鼠随机分为3组:正常对照组(NC组)、糖尿病模型组(DM组)、糖尿病模型+厄贝沙坦(50mg·kg-1)组(DI组)。后2组腹腔注射链脲佐菌素诱导大鼠建立糖尿病模型后DI组灌胃厄贝沙坦。8周后,用免疫组化方法(SP法)和逆转录-聚合酶链反应法(RT-PCR)检测各组大鼠肾皮质MMP-2、TIMP-2及Ⅳ-C的表达。结果:与NC组比较,DM组大鼠肾小球MMP-2蛋白、mRNA的表达明显降低,TIMP-2及Ⅳ-C蛋白、mRNA明显增强(P<0.01),出现糖尿病肾病典型的病理改变。与DM组比较,DI组MMP-2蛋白、mRNA表达明显增强(P<0.01),TIMP-2和Ⅳ-C表达明显降低(P<0.01)。结论:厄贝沙坦可能通过调节MMP-2/TIMP-2的平衡,减少细胞外基质Ⅳ-C积聚而发挥对糖尿病大鼠的肾脏保护作用。     

姜黄素对糖尿病大鼠肾脏TGF-β1影响及保护性研究

目的观察糖尿病大鼠肾脏TGF—β1表达及姜黄素胶囊的治疗作用。方法采用STZ注射法制作糖尿病（DM）大鼠模型,随机分为正常组,DM组,姜黄素组。灌胃给药8周后,采用免疫组化等方法测定24h尿白蛋白排泄率（UAER）、肾小球滤过率（GFR）、肾皮质TGF-β1、FN、Col—Ⅳ的表达。结果（1）功能学变化：姜黄素组大鼠的24hUAER和GFR显著低于DM、对照组,差异有统计学意义（P〈0．05）。（2）免疫组化：姜黄素组大鼠肾皮质TGF—β1、FN、Col—Ⅳ的表达显著低于DM组,差异有统计学意义（P〈0．05）。结论姜黄素胶囊有降低早期糖尿病肾病大鼠尿白蛋白排泄率及减少过高的GFR、抑制‘肾组织增生、抑制。肾皮质TGF-β1、FN、Col—Ⅳ表达等保护作用。     

姜黄素对糖尿病大鼠肾脏保护作用的机制研究

目的 探讨姜黄素对实验性糖尿病大鼠肾脏基质金属蛋白酶-2（matrix metalloproteinase-2,MMP-2）及其抑制物金属蛋白酶-2组织抑制物（tissue inhibitor of metalloproteinase-2,TIMP-2）表达的影响.方法 大鼠随机分为正常对照组（A组）、糖尿病组（B组）及姜黄素治疗组（C组）,采用腹腔单剂量注射链脲佐菌素（streptozotocin,STZ）65 mg/kg建立糖尿病大鼠模型.治疗组给予姜黄素30 mg·kg-1·d-1腹腔注射.实验第3、6周各组分别宰杀6只大鼠,并检测24 h尿白蛋白排泄率（urinary albumin excretion rate,UAER）、肌酐清除率（creatinine clearance rate,Ccr）及肾重/体重.采用免疫组织化学染色法检测肾小球MMP-2、TIMP-2、纤维连接蛋白（fibronectin,FN）和Ⅳ型胶原表达.结果 治疗组大鼠UAER（P〈0.05或〈0.01）、Ccr（P〈0.05）、肾重/体重（P〈0.05）均明显低于糖尿病组大鼠.免疫组织化学染色可见糖尿病大鼠肾小球TIMP-2、 FN和Ⅳ型胶原表达均明显增加（P〈0.05或〈0.01）,治疗组上述指标的表达均受到明显抑制（P〈0.05）.MMP-2在糖尿病大鼠肾小球的表达明显被抑制（P〈0.01）,治疗组其表达明显增加（P〈0.05）.结论 姜黄素通过上调糖尿病大鼠肾小球MMP-2表达、下调TIMP-2表达,对糖尿病大鼠肾脏病变具有保护作用.     

贝那普利对糖尿病大鼠心肌细胞外基质重塑中基质金属蛋白酶及转化生长因子表达的影响

目的研究贝那普利对糖尿病大鼠心肌基质重塑的作用机制。方法 SD大鼠ip注射链脲佐菌素制备糖尿病模型。治疗组ig给予BZ 10 mg.kg-1,连续12周。光镜及电镜下观察左心室心肌组织改变,测定心脏质量指数;Western印迹法测定左心室心肌组织胶原Ⅰ型及Ⅲ型含量,基质金属蛋白酶2(MMP-2),金属蛋白酶组织抑制因子2(TIMP-2)表达及转化生子因子β1(TGF-β1)和结缔组织生长因子(CTGF)表达的变化。结果与正常对照组相比,糖尿病组大鼠心脏质量指数明显升高,胶原Ⅰ型及Ⅲ型表达明显增加(P<0.05),MMP-2表达减少、TIMP-2表达增加(P<0.01),TGF-β1和CTGF表达明显增强(P<0.05),心肌间质纤维增生。大鼠连续ig给予贝那普利12周后,心脏质量指数明显降低〔(4.13±0.18)vs(3.42±0.13)mg.g-1〕;胶原Ⅰ型及Ⅲ型表达明显减少(P<0.05),MMP-2表达增加,TIMP-2表达减少(P<0.05),TGF-β1及CTGF表达明显减弱(P<0.05),心肌间质纤维增生减轻。与正常对照组相比,贝那普利组大鼠心肌MMP-2表达减少,TIMP-2及CTGF表达仍增加。结论贝那普利可能通过抑制糖尿病大鼠心肌组织TGF-β1和CTGF表达以及增强基质金属蛋白酶表达,从而抑制糖尿病心肌间质纤维化,改善心肌细胞外基质重塑。     

氨基胍对糖尿病大鼠肾损害的治疗作用

目的通过探讨氨基胍（AG）对早期糖尿病（DM）大鼠一氧化氮（NO）、一氧化氮合酶（ni-tric oxi desynthase,NOS）活性及24h尿蛋白排泄量（24hUPE）的影响,了解氨基胍对糖尿病肾病的治疗作用。方法健康清洁级Wistar大鼠40只,检测24hUPE、血清NO水平、总一氧化氮合酶（total nitric oxide synthase,tNOS）和诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）及结构型一氧化氮合酶（constructive nitric oxide synthase,cNOS）活性等5项指标后,用链脲佐菌素（Streptozotocin,STZ）60mg/kg制备成糖尿病大鼠模型,将糖尿病鼠随机分为糖尿病对照组、氨基胍组（AG组）。于8周末时再检测大鼠的上述5项指标并进行统计分析。结果①与造模前比较,DM对照组在8周末时24hUPE、NO和iNOS升高（P〈0.01,P〈0.05）;AG组24hUPE增加（P〈0.01）,tNOS、iNOS、cNOS降低（P〈0.01,P〈0.05）。②与DM对照组比较,8周末时AG组5项指标均下降（P〈0.05）。结论在糖尿病肾病（DN）的发展进程中,早期阶段应用AG可通过降低血NOS活性、NO生成量及其他机制,使24hUPE减少,减轻肾脏的损害。     

血清同型半胱氨酸与胱抑素C在2型糖尿病肾病患者中的变化意义分析

目的 在临床上对2型糖尿病合并肾病患者的血清同型半胱氨酸（Homocysteine,Hcy）水平和胱抑素C （Cystatin C,Cys C）水平进行测定,并探讨两指标在临床诊断中的价值.方法 回顾我院自选2011年6月至2013年6月间在我院进行治疗的184例糖尿病患者的病例.参照患者临床尿清白蛋白（UAER）水平分为糖尿病无肾病组（86例）和糖尿病合并肾病组（98例）,并选择90例健康体检者作为对照组.对三组的Hcy、Cys C和UAER的水平进行测定和对比分析.结果 糖尿病合并肾病患者的Hcy、Cys C和UAER水平分别为（22.48±2.42）μmol/L、（2.37±0.92） mg/L和（365.41±62.85） mg/24 h显著性的大于糖尿病无肾病患者（8.13±2.01）μmol/L、（1.01±0.62） rng/L和（36.47±10.26） mg/24 h和健康对照组（7.01±1.46）μmol/L、（0.91±0.59） mg/L和（29.41±8.58） mg/24 h,（P＜0.05）.而糖尿病无肾病患者的Hcy、Cys C和UAER水平略大于对照组患者,但两组间差异无统计学意义（P＞0.05）.多元线性分析结果表明：糖尿病合并肾病患者的Hcy、Cys C和UAER成正相关性（r=0.281、0.312,P＜ 0.05）.结论 Hcy和Cys C可作为临床诊断患者糖尿病状况的有效指标,联合使用能显著提升诊断的准确率.     

2型糖尿病肾病患者血清C肽水平变化的意义

目的 探讨2型糖尿病肾病患者血清C肽水平变化的意义.方法 选取住院2型糖尿病患者120例,按尿白蛋白排泄率大小分成3组,正常白蛋白尿组34例,微量白蛋白尿组40例,临床白蛋白尿组46例,同时设血糖正常健康组30例.测各组空腹血糖、糖化血红蛋白(HbA1c)、空腹血清C肽(FCP),并进行比较分析.结果 微量白蛋白尿组和临床白蛋白尿组患者血清C肽与正常健康组比较,差异有统计学意义[(1.27±0.5)μg/L和(0.32±0.16)μg/L比(2.39±0.22)μg/L,P＜0.01];血清C肽水平与尿白蛋白排泄率呈负相关(r=-0.745,P＜0.01).结论 血清C肽水平的下降可能参与2型糖尿病肾病发生发展.

Abstract：

Objective To investigate the change of serum C-peptide level in type 2 diabetic nephrosis patients. Methods We recruited 120 patients with type 2 diabetes. The level of fasting plasma glucose (FBG), glycated hemoglobin (HbA1c), fasting C-peptide (FCP) and urinary albumin excretion rate (UAER) were measured.According to UAER, 120 patients were divided into Group Ⅰ: normal albuminuria group, 34 patients; Group Ⅱ:microalbuminuria group, 40 patients; Group Ⅲ: clinical albuminuria, 46 patients. At same time, we selected 30 healthy people as control group. Results The level of C-peptide decreased significantly in Group Ⅱ and Group Ⅲ compared with that of control group (P ＜0.01 ). The difference of C-peptide level between Group Ⅱ, Group Ⅳ and Group Ⅰ was statistically significant (P ＜ 0.01 ). The level of C-Peptide and urinary albumin excretion rate was negatively correlated (R = -0. 745 ,P ＜ 0. 01 ). Conclusion The decline of serum C-pcptide may be involved in the development of type 2 diabetic nephropathy.     

缬沙坦和前列地尔联合治疗糖尿病肾病的疗效研究

目的 观察缬沙坦和前列地尔联合治疗糖尿病肾病的临床疗效.方法采用随机、双盲、平行的方法将糖尿病肾病患者90例分为3组,每组30例,分别进行单用缬沙坦(80～160 mg/d),单用前列地尔(10 μg/d)以及联合缬沙坦(80～120 mg/d)和前列地尔(10 μg/d)治疗,血压均控制在125/75mmHg以下,疗...     

来氟米特对糖尿病肾病大鼠RANTES与FOXP3表达的影响

目的:观察RANTES、FOXP3、ED-1在肾组织中的蛋白表达,探讨LEF对糖尿病肾病肾组织炎症反应及病理改变的影响。方法:35只雄性Wistar大鼠随机分为正常对照组N(n=10)、模型DN(n=13)、来氟米特组DD(n=12)。采用弗氏完全佐剂(CFA)和链脲佐菌素(STZ)制备糖尿病肾病模型。检测24 h尿蛋白定量,HE染色观察肾脏组织学改变,免疫组织化学方法检测肾组织RANTES、FOXP3、ED-1表达。结果:与对照组比较,模型组24 h尿蛋白排泄量显著上升(P<0.05),模型组大鼠肾组织肾小球肥大、肾小管上皮细胞变性或脱落、单核/巨噬细胞浸润、肾间质病变等病理变化明显;模型组大鼠肾组织内RANTES、FOXP3、ED-1表达均明显增强(P<0.05);与模型组比较,LEF治疗组大鼠24 h尿蛋白下降,肾组织RAN-TES、FOXP3、ED-1表达显著减少,肾脏病理改变有所减轻。结论:LEF可能是通过抑制RANETS、FOXP3、ED-1在肾组织中的表达,减少炎症细胞在肾组织中的浸润,对延缓糖尿病肾病的发展具有一定的作用。     

Inhibition of both neutral endopeptidase and endothelin-converting enzyme by SLV306 reduces proteinuria and urinary albumin excretion in diabetic rats

Diabetic nephropathy is a serious complication of diabetes associated with a poor prognosis which deteriorates to end-stage renal disease. Increased urinary excretion of protein and albumin are early clinical markers for diabetic renal disease and increased risk of cardiovascular disease. Diabetes causes activation of the renal endothelin system inducing renal damage. We analyzed the effects of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on diabetes-induced alterations of kidney function and morphology in rats with streptozotocin-induced diabetes. The effects of SLV306 (30 mg/kg per day), captopril (10 mg/kg per day), and placebo on urinary protein and albumin excretion as well as on blood pressure were studied in diabetic rats in comparison to non-diabetic control rats. The rats were treated for 20 weeks. At the end of the study kidney morphology was also analyzed using computer-aided image analysis systems. Serum glucose and blood pressure were similar in all diabetic groups. No side-effects were observed with SLV306 and captopril treatment. Protein excretion was 17.3 +/- 3.0 mg/24 hours in untreated diabetic rats. Protein excretion decreased significantly in the SLV306 (4.8 +/- 0.9 mg/24 hours; P = 0.03 vs untreated diabetic rats) as well as in the captopril (5.1 +/- 1.0 mg/24 hours; P = 0.03 vs untreated diabetic rats) -treated diabetic rats. Albumin excretion was 0.51 +/- 0.12 mg/24 hours in the untreated diabetic group and decreased likewise in the SLV306-treated diabetic rats (0.09 +/- 0.03 mg/24 hours; P = 0.04 vs untreated diabetic rats). The captopril-treated diabetic rats showed a strong trend towards reduced albumin excretion (0.12 +/- 0.04 mg/24 hours; P = 0.06 vs untreated diabetic rats). Computer-aided image analysis revealed that renal interstitial matrix content was significantly decreased in diabetic rats treated with either the angiotensin-converting enzyme inhibitor or the neutral endopeptidase/endothelin-converting enzyme inhibitor as compared to untreated diabetic rats. It was found that SLV306 decreases renal matrix protein content as well as protein and albumin excretion in diabetic rats independent of blood pressure. These effects are comparable to those of angiotensinconverting enzyme inhibition.