雷公藤多苷对糖尿病肾病大鼠肾脏中CTGF表达的影响

目的：观察糖尿病肾病（DN）大鼠经雷公藤多苷干预后,肾皮质中结缔组织生长因子（connective tissue growth factor,CTGF）表达的变化,并探讨雷公藤多苷在其中的作用。方法：Wister大鼠48只,随机分为正常对照组、DN组与雷公藤多苷治疗组。DN组与雷公藤多苷治疗组大鼠分别给予链脲佐菌素（STZ）55mg／kg一次性腹腔注射建立糖尿病大鼠模型。模型建立后第4、8、12周各组分别处死4只大鼠并收集标本,记录体重、检测血糖、血肌酐、尿素氮、胆固醇、三酰甘油、24h尿蛋白定量。用RT-PCR法检测肾皮质CTGF mRNA含量表达水平。结果：（1）DN组大鼠血糖、血肌酐、血尿素氮、血胆固醇、血三酰甘油、24h尿蛋白定量均明显高于正常对照组（P〈0．01）;肾组织CTGFmRNA的表达量明显高于正常对照组（P〈0．01）。（2）雷公藤多苷治疗组血糖、血肌酐、血尿素氮、血胆固醇、血三酰甘油及24h尿蛋白定量在第12周与DN组比较均有统计学差异（P〈0．01）;治疗组肾组织CTGFmRNA含量的表达明显低于DN组（P〈0．01）。结论：雷公藤多苷可减少DN大鼠尿蛋白的排泄及降低血尿素氮、血肌酐,明显降低肾组织CTGFmRNA表达量,提示雷公藤多苷能有效延缓DN进展,并有一定的保护作用。     

阿魏酸钠对糖尿病肾病的保护作用及机制

目的：观察阿魏酸钠对糖尿病肾病伴高脂血症患者血脂、内皮素、一氧化氮、24h尿蛋白的影响。方法：将60例糖尿病肾病伴高脂血症患者随机分为治疗组（30例）和对照组（30例）,两组基础治疗相同,治疗组在对照组基础治疗上加用阿魏酸钠,治疗4周后观察两组患者血脂、内皮素、一氧化氮、24h尿蛋白及临床症状的变化。结果：与对照组比较,治疗组在降低总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、内皮素（endothelin,ET）、24h尿蛋白和升高一氧化氮（nitric oxide,NO）方面疗效更为显著,两组升高高密度脂蛋白胆固醇（HDL-C）的疗效相似。结论：阿魏酸钠可有效调节糖尿病肾病伴高脂血症患者血脂水平,改善内皮功能,降低尿蛋白,对糖尿病肾病有保护作用。     

肾囊注射甲泼尼龙快速诱导缓解原发性重症肾病综合征临床研究

目的：研究肾囊注射甲泼尼龙在快速诱导缓解原发性重症肾病综合征（nephroticsyndrome,NS）中的疗效与安全性。方法：将原发性重症NS患者32例随机分为肾囊注射组20例及对照组12例,常规行肾脏穿刺病理检查。在共同基础治疗的前提下,肾囊注射组采用甲泼尼松0.5mg·kg-1.d-1口服加肾囊注射40mg/每侧肾囊,每周2次,共5周;对照组采用泼尼松1.0mg·kg-1.d-1,不加肾囊注射,共观察12周。分别于治疗前,研究过程的第3、6、9、12周记录两组的体重、血浆白蛋白、24h尿蛋白定量、血清肌酐的变化及相应并发症。结果：肾囊注射组第3、6、9、12周及对照组第9、12周时体重、血浆白蛋白、24h尿蛋白与治疗前基础数值相比差异均有统计学意义（P〈0.05）;两组血肌酐治疗前后差异均无统计学意义（P〉0.05）;治疗组与对照组在研究的第3、6周时体重、血浆白蛋白、24h尿蛋白相比较存在差异并具有统计学意义（P〈0.05）;两组在研究第9周时血浆白蛋白、24h尿蛋白相比较差异有统计学意义（P〈0.05）;12周时两组间各项观察指标变化的差异不大（P〉0.05）。肾脏病理类型中,微小病变型和系膜增生型对甲泼尼龙注射效果最佳,膜型肾病次之,有慢性化倾向或伴膜增殖者疗效差。结论：肾囊注射甲泼尼龙治疗原发肾病综合征是安全有效的,能够快速诱导肾病综合征临床症状的缓解。     

益肾胶囊对糖尿病肾病大鼠模型肾组织TLR4表达的影响

目的：观察益肾胶囊对糖尿病肾病（DN）大鼠模型肾组织Toll样受体4（toll-like receptor4,TLR4）、白细胞介素-6（IL-6）及白细胞介素-8（IL-8）表达水平的影响。方法：36只Wistar雄性大鼠随机分成正常对照组、DN模型组、益肾胶囊治疗组,每组12只,利用单侧肾切除加腹腔注射链脲佐菌素建立DN大鼠模型,连续给药12周。记录大鼠体重、观察24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）变化;取肾组织行病理组织学观察;用免疫荧光方法检测肾组织中TLR4、IL-6及IL-8的表达水平的变化。结果：12周末,DN模型组大鼠的24h尿蛋白定量、Scr、BUN均高于正常对照组（P〈0.05）,肾组织中TLR4、IL-6及IL-8表达水平明显高于正常对照组（P〈0.05）;益肾胶囊治疗组大鼠24h尿蛋白定量、Scr、BUN均低于模型组（P〈0.05）,肾组织TLR4、IL-6及IL-8表达水平明显低于DN模型组（P〈0.05）。结论：益肾胶囊可能通过调节肾组织TLR4、IL-6及IL-8的表达,减少DN的炎症反应,从而延缓了DN的进展。     

前列地尔联合甲钴胺治疗糖尿病周围神经病变的疗效分析

目的探讨前列地尔联合甲钴胺治疗糖尿病周围神经病变的疗效。方法选择72例确诊的糖尿病周围神经病变患者作为观察对象，随机分为观察组和对照组各36例。两组同时给予维生素B1 10mg，甲钻胺500μg，肌肉注射，1次，d，连用4周。其中治疗组在上述基础上给予前列地尔注射液10u＋生理盐水10mL静脉推注，1次／d，疗程2周；观察两组患者治疗前后的疗效，并监测血糖、血压、肝肾功能、血尿常规等情况。结果观察组的总有效率（91．7％）明显高于对照组（75．0％），差异有统计学意义（P〈0．05）。结论前列地尔联合甲钴胺治疗糖尿病周围神经病变疗效确切，不良反应少，安全性好，值得推广和应用。     

黄葵胶囊联合厄贝沙坦治疗慢性肾小球肾炎的临床观察

目的：探讨黄葵胶囊联合厄贝沙坦治疗慢性肾炎的临床疗效。方法：将60例肾功能正常的慢性肾炎患者随机分为厄贝沙坦组（对照组）和黄葵胶囊联合厄贝沙坦组（治疗组）,对照组主要是在对症治疗基础上采用厄贝沙坦治疗,治疗组为在对照组治疗基础上加用黄葵胶囊治疗,观察时间为12周,分别检测两组治疗前后24 h尿蛋白定量、血压、血肌酐等。结果：治疗12周后治疗组临床疗效总有效率（86.67%）显著高于对照组（56.67%）（P〈0.05）,治疗组的24 h尿蛋白定量低于对照组（P〈0.05）;两组血压、血肌酐差异无统计学意义（P〉0.05）。结论：黄葵胶囊联合厄贝沙坦治疗可有效地降低慢性肾炎患者蛋白尿。     

益肾胶囊对糖尿病肾病大鼠肾组织炎症因子NF-κB的影响

目的：观察益肾胶囊对糖尿病肾病（DN）大鼠肾组织核转录因子-κB（nuclear factor-κB,NF-κB）表达的影响。方法：将40只健康雄性Wistar大鼠随机分为：正常对照组（对照组）、DN模型组（模型组）、氯沙坦组、益肾胶囊组,每组10只。利用链脲佐菌素（STZ）诱导右肾切除的大鼠制备DN模型。氯沙坦组灌胃氯沙坦钾20mg·kg-1.d-1,益肾胶囊组灌胃益肾胶囊625mg·kg-1.d-1,对照组及模型组每日给予等量的蒸镏水灌胃,实验周期为12周。实验过程中观察大鼠24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）变化,光镜下观察肾脏病理变化,采用免疫荧光法检测各组大鼠肾组织NF-κB的表达。结果：12周末,DN模型组大鼠的24h尿蛋白定量、Scr、BUN均高于正常对照组（P〈0.05）,肾组织中NF-κB表达水平明显高于正常对照组（P〈0.05）;益肾胶囊治疗组大鼠24h尿蛋白定量、Scr、BUN均低于模型组（P〈0.05）,肾组织NF-κB表达水平明显低于DN模型组（P〈0.05）。结论：益肾胶囊可能通过下调DN大鼠肾脏组织NF-κB的表达,延缓DN的进展。     

马来酸依那普利叶酸治疗H型高血压93例

目的观察马来酸依那普利叶酸治疗伴有同型半胱氨酸（Hcy）升高高血压（H型高血压）的临床疗效。方法H型高血压患者185例,随机分为治疗组93例和对照组92例,治疗组给予马来酸依那普利叶酸片（10 mg＋0.8 mg·d－1,qd）,对照组给予马来酸依那普利片（10 mg·d－1,qd）,治疗24周。观察服药前及服药后24周末血压、血压变异性（BPV）、血浆Hcy、颈动脉内膜厚度（IMT）变化。 结果治疗24周后,两组血压均显著下降（P＜0.05）;治疗组治疗24周末24 h平均收缩压（24 hSBP）、24 h平均舒张压（24 hDBP）、白昼收缩压（dSBP）较对照组降低（P＜0.05）。两组治疗24周末24 hSBPV、dSBPV、nSBPV、24 hDBPV、dDBPV、nDBPV均较治疗前显著降低（P＜0.05）;治疗组治疗24周末24 hSBPV、dSBPV 、24 hDBPV、dDBPV低于同时间点对照组（P＜0.05）。治疗组血浆Hcy水平显著降低,与对照组比较,差异有统计学意义（P＜0.01）。治疗组IMT水平较对照组明显降低,差异有统计学意义（P＜0.05）。结论马来酸依那普利叶酸片能有效改善H型高血压患者血压、血压变异性、血浆Hcy、IMT水平,延缓动脉硬化进程。     

温肾健脾、活血通络法干预糖尿病肾病Ⅳ期尿蛋白及肾功能的临床研究

目的：以理论研究与临床研究相结合的方法，观察温肾健脾、活血通络中药复方对糖尿病肾病Ⅳ期尿蛋白及肾功能的影响。方法：我们对120例糖尿病肾病（DN）患者进行了随机对照研究，以观察其对 DN 的保护作用。结果：本研究收集病例80例，治疗组40例，对照组40例，治疗组可明显改善 DN 患者倦怠乏力、气短懒言、腰膝酸软，且治疗组疗效优于对照组（P ﹤0．01）。治疗组治疗后24 h 尿蛋白定量较前明显降低，血浆白蛋白升高（P ﹤0．01）。治疗组治疗前后血肌酐、肾小球滤过率无明显变化（P ﹥0．05），而对照组 Scr 与 GFR 水平相对治疗前均有明显变化（P ﹤0．01）。治疗过程中，两组血糖、糖化血红蛋白均控制在规定范围内，同时也排除血糖过高对 UAE 的影响。两组试验过程中未发现任何不良反应。结论：温肾健脾、活血通络中药复方可减少临床期 DN 患者24 h 尿蛋白，改善患者营养状态，保护肾功能，干预 DN 进展。     

黄葵胶囊治疗难治性膜性肾病的临床疗效观察

目的：观察黄葵胶囊治疗难治性膜性肾病的疗效。方法：将我院经激素标准疗程加环磷酰胺冲击治疗半年无效的难治性膜性肾病患者30例,采用随机数字表法分为治疗组和对照组,治疗组给予黄葵胶囊和泼尼松治疗14例,对照组给予泼尼松治疗16例。观察用药前后患者24 h尿蛋白定量、血清白蛋白、血肌酐、血谷丙转氨酶的变化,及两组治疗总有效率等,同时记录不良反应。结果：治疗24周后,两组总有效率为（治疗组vs对照组：92.9%vs 56.3%）,两组间差异有统计学意义（P〈0.05）;治疗组治疗4、12和24周时24 h尿蛋白定量较对照组治疗同期减少,差异有统计学意义（P〈0.05）。结论：黄葵胶囊治疗难治性膜性肾病能有效降低尿蛋白。     

The treatment of tacrolimus in primary IgA nephropathy with mild or moderate renal injury: a randomized controlled study

Objective To investigate the efficacy and safety of immunosuppressive therapy (Tacrolimus or CTX) in primary IgA nephropathy (IgAN) with mild or moderate renal dysfunction. Methods Thirty-six primary IgAN patients diagnosed by renal biopsy, with mild or moderate renal dysfunction[30 ml•min-1•(1.73m2)-1≤eGFR＜90 ml•min-1•(1.73m2)-1, proteinuria＞1.0 g/24 h] were recruited in this randomized controlled trial. All the patients were assigned into steroid therapy alone, steroid combined with CTX (CTX group) and steroid combined with tacrolimus (tacrolimus group). Results The 24-hour proteinuria at baseline were (1.91±0.81) g/24 h, (2.42±1.46) g/24 h, (2.57±1.87) g/24 h in steroid group, CTX group and tacrolimus group respectively. Compared with baseline, it was significantly decreased in steroid group at 3 months [(0.90±0.75) g/24 h, P＜0.05], 6 months [(0.76±0.73) g/24 h, P＜0.05] and 12 months [(0.35±0.35) g/24 h, P＜0.05], in CTX group at 3 months [(1.40±1.24) g/24 h, P＜0.05], 6 months [(0.87±0.83) g/24 h, P＜0.05] and 12 months [(0.68±0.70) g/24 h, P＜0.05], and in FK506 group at 3 months [(1.10±1.33) g/24 h, P＜0.05], 6 months [(0.78±0.69) g/24 h, P＜0.05] and 12 months [(0.69±0.82) g/24 h, P＜0.05]. At 6 months, serum creatinine were decreased in steroid alone [(111.72±31.23) μmol/L vs (121.17±36.51) μmol/L, P＜0.05] and in CTX group [(111.33±22.76) μmol/L vs (124.33±35.51) μmol/L, P＜0.05], while no significant difference was detected in tacrolimus group. At 12 months, there was no significant difference in terms of serum creatinine in all three groups. Besides, there was no significant difference in terms of eGFR (CKD-EPI) in all three groups. One case presented hyperglycemia and one case had liver dysfunction during the treatment in steroid group. Two cases had hyperglycemia, one case had impaired glucose tolerance and one case had liver dysfunction in the tacrolimus group. Conclusions Steroid along, steroid combined with tacrolimus or combined with CTX are efficient in reducing urine protein in the treatment of primary IgAN with mild or moderate renal dysfunction without inducing increased serum creatinine. Given the occurrence of hyperglycemia during the treatment with steroid combined with tacrolimus, it is important to monitor tacrolimus concentration during the treatment.     

The mechanism of focal necrotizing glomerulonephritis induced by FimH fusion protein

Objective To investigate the mechanism of focal necrotizing glomerulonephritis induced by FimH fusion protein. Methods Wistar-Kyoto (WKY) rats were immunized with purified FimH fusion protein (150 μg) emulsified in Titermax Gold. Controls received PBS in Titermax Gold alone. Glomerular injuries were assessed by 24-hour urinary protein, urea nitrogen (BUN), serum creatinine (Scr), serum uric acid (UA) and histomorphology. The levels of interleukin-17A (IL-17A) were detected by ELISA assay. Results The levels of 24-hour urinary protein began to rise at 3rd day after immunization with FimH fusion protein, and were significantly higher than control group on 7th , 35th and 50th day [(8.59±1.25) mg vs (3.08±1.08) mg, (10.33±1.10) mg vs (6.40±0.61) mg, (12.45±1.73) mg vs (5.93±0.83) mg, all P＜0.05].The serum levels of BUN, Scr, UA in model rats were increased significantly at 50th day [(6.76±0.20) mmol/L vs (5.82±0.13) mmol/L, (58.00±1.53) μmol/L vs (25.67±1.45) μmol/L,(61.67±7.27) μmol/L vs (31.33±2.73) μmol/L, all P＜0.05] compared to control group. WKY rats immunized with FimH fusion protein showed segmental necrosis of glomerular capillaries, alveolar wall thickening, and significant inflammatory cells infiltration on 35 th day, and glomerular crescent formation after 50 days. The serum levels of IL-17A were increased significantly compared to control group on 35th and 50th day [(46.97±5.00) ng/L vs (11.27±2.67) ng/L, (41.95±5.51) ng/L vs (16.31±1.64) ng/L, P＜0.05]. The IL-17A level was positively correlated with 24-hour urinary protein in model group (r＝0.557, P＝0.021). Conclusion Bacteria FimH protein can induce glomerular focal necrotic lesion and lung injury in WKY rats, and IL - 17Amay involve in the damage process.     

Pharmacological Dose of Vitamin B12 Is as Effective as Low-Dose Folinic Acid in Correcting Hyperhomocysteinemia of Hemodialysis Patients

Various regimens of folic acid-based and vitamin B12 (Vit B12) supplementations have been tried for lowering plasma homocysteine (Hcy) levels in uremic patients. However, the therapeutic potency of low-dose folic acid and Vit B12 alone is not properly understood. In this study, seventy-five patients on chronic hemodialysis (HD) therapy were randomized into three groups. The FNA group received intravenous (IV) supplementation with folinic acid 3 mg weekly; the Vit B12 group received IV supplementation with vitamin B12 1 mg weekly; and the combination group received IV supplementation with both agents weekly. Blood levels of Hcy, folic acid, and Vit B12 were measured monthly for three months. After three months of treatment, plasma levels of Hcy decreased significantly in all three groups when compared with their baselines (all p < 0.05). The final Hcy level was significantly lower in the combination group (11.5 ± 2.3 μmol/L) when compared with that of the FNA group (15.9 ± 5.6 μmol/L, p < 0.05) but not with the Vit B12 group (15.9 ± 11.6 μmol/L), although their baseline levels were similar. The percentage decreases of tHcy at the end of the treatment in the FNA group, Vit B12 group, and combination group were 16.4%, 29.3%, and 38.9% respectively. Our study showed that IV pharmacologic dose of Vit B12 alone is as effective as low-dose folic acid in correcting hyperhomocysteinemia in chronic HD patients, and combining both drugs in low doses may have added effects.     

Effect of gender matching on the outcomes of living-donor renal transplantation

Objective To evaluate the effect of gender matching on the outcomes of living-donor renal transplantation. Methods A total of 419 cases of living-donor renal transplantation in our center were divided into male-donor-male-recipient (MDMR) group, male-donor-female-recipient (MDFR) group, female-donor-male-recipient (FDMR) group, female-donor-female-recipient (FDFR) group. The outcomes including graft and patient survival, acute rejection and renal function were analyzed retrospectively. Results Compared to MDMR group, MDFR group and FDFR group had lower Scr [(80.7±17.9), (87.4±21.9) μmol/L vs (120.3±72.5) μmol/L, all P＜0.05] and uric acid (UA) [(318.1±86.4), (303.5±66.9) μmol/L vs (358.4±77.8) μmol/L, P＜0.05] 6 months after operation. Compared to MDFR group, FDMR group had higher Scr[(117.7±27.4) μmol/L vs (80.7±17.9) μmol/L, P＜0.01], UA [(371.0±92.4) μmol/L vs (318.1±86.4) μmol/L, P＜0.05] and lower glomerular filtration rate (GFR) [(70.4±17.8) ml/min vs (79.6±18.9) ml/min, P＜0.05]. Compared to FDMR group, FDFR group had lower Scr [(87.4±21.9) μmol/L vs (117.7±27.4) μmol/L, P＜0.01] and UA [(303.5±66.9) μmol/L vs (371.0±92.4) μmol/L, P＜0.01]. Compared to MDFR group, FDFR group showed lower GFR [(72.4±25.3) ml/min vs (82.7±18.7) ml/min, P＜0.05] 1 year after operation. Compared to MDMR group, FDFR group showed lower UA [(322.9±69.7) μmol/L vs (376.0±66.2) μmol/L, P＜0.05] 2 years after operation. Compared to FDMR group, FDFR group showed lower Scr [(88.7±27.0) μmol/L vs (112.7±27.8) μmol/L, P＜0.05] and UA [(318.3±61.2) μmol/L vs (396.2±100.3) μmol/L, P＜0.05] 3 years after operation. 5 years after operation, there were no significant differences in above indexes, the incidence of slow graft function, acute rejection and survival of graft and patient among groups. Conclusions Male recipients of female donors have the worst renal function while female recipients have better outcomes after operation.     

Role of inhibitor of nuclear factor kappa B kinase alpha on renal inflammation after ischemia-reperfusion injury and its associated mechanism

Objective To reveal the role of inhibitor of nuclear factor kappa B kinase alpha(IKKα) in renal inflammation after renal ischemia-reperfusion （IR） injury and its potential associated mechanism. Methods Ischemia-reperfusion injury models were induced in a total of 24 healthy C57BL/6 male mice. Renal function and histological changes were estimated. The expression and site of IKKα, p52, RelB, IL-10 and IL-18 were determined by immunohistochemistry and Western blotting. After the short hairpin RNA(shRNA)targeting IKKα was injected into renal parenchyma, renal function and protein expressions of IKKα, p52, RelB, IL-10, IL-18 were detected. Results Compared with sham-operated group[Scr(7.30±0.13) μmol/L, BUN (8.39±0.30) mmol/L], levels of Scr [(29.80±2.10) μmol/L, (27.00±3.40) μmol/L, (23.00±3.70) μmol/L] and BUN [(9.47±3.50) mmol/L, (11.68±4.30) mmol/L, (13.12±2.10) mmol/L] were higher on day 1, 3, 7 and the injury of kidney was serious in IR injury group. Immunohistochemical expression of both IL-18 and IL-10 were increased. Markedly increased IKKα, p52 and RelB protein expression were noted in experiments from day 1 to day 7 during kidney recovery period, with a peak on day 3 and then decreasing toward baseline after day 7. Compared with IR injury group, low-expression of IKKα by injection of shRNA up-regulated the expression of IL-18 and down-regulated the expression of IKKα, p52, RelB and IL-10. Conclusions The NF-κB pathway is activated and IKKα expression is up-regulated during the kidney ischemia-reperfusion injury, low-expression of IKKα may block inflammation resolution via down-regulation of alternative NF-κB pathway family members of both p52 and RelB.     

Protective effect of resveratrol on 5/6 nephrectomized rats and its mechanism

Objective To investigate the protective effect of resveratrol (RSV) on 5/6 nephrectomized rats and its mechanism. Methods Fifty male SD rats were randomly divided into three groups: sham operated (Sham, n＝10）, 5/6 nephrectomy (Nx, n＝20), and 5/6 nephrectomy＋RSV 20 mg/kg (Nx＋RSV, n＝20). RSV or normal saline was administered one week after 5/6 nephrectomy. Proteinuria was detected every 4 weeks. Serum creatinine and the renal pathological changes were measured after 12 weeks. Immunohistochemisty staining of fibronectin (FN), collagenⅠ, transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) were used to analyze the changes of renal fibrosis. Western blotting was used to measure the expression of Smad3, phospho-Smad3, and acety-Smad3. Immunoprecipitation was used to detect the interaction between Sirt1 and Smad3. Results Compared with the sham operated rats, subtotal nephrectomy significantly increased proteinuria [(152.14±30.49) mg/24 h vs (25.34±7.54) mg/24 h], serum creatinine[(111.60±21.50) μmol/L vs (53.90±11.59) μmol/L], glomerular sclerosis index (1.56±0.34 vs 0.35±0.08) and the expressions of fibronectin, collagenⅠ, TGF-β and CTGF in renal tissue at 12 weeks after operation (all P＜0.01), and RSV treatment significantly inhibited the above up-regulations (all P＜0.01). Compared with the sham operated rats, subtotal nephrectomy increased the expression of phospholylation and acetylation of Smad3. RSV treatment significantly reduced the expression of acety-Smad3, but had no effect on the phospho-Smad3. Immunoprecipitation revealed a binding effect of Smad3 with Sirt1. Conclusions RSV treatment can attenuate proteinuria, protect renal function and inhibit renal fibrosis in 5/6 nephrectomized rats. This renal protective effect is associated with reduced Smad3 acetylation and activation of Sirt1, which suggesting that Sirt1 may be a potential therapeutic target of CKD.     

Effects of irbesartan on the expression of hypoxia-induced factor 1α and connective tissue growth factor in the kidney of unilateral ureteral ligation operation model rats

Objective To investigate the expression of hypoxia-induced factor 1α (HIF-1α)and connective tissue growth factor (CTGF) in the kidneys of unilateral ureteral ligation operation (UUO)model rats and the effect of irbesartan on the expression. Methods Thirty healthy adult male SD rats were randomly divided into 3 groups: sham operation group (n＝10), UUO group (n＝10) and irbesartan group (n＝10, UUO rats treated with irbesartan by lavage 2 days before operation). The rats in sham group and UUO group were treated with equal normal saline by lavage. Renal function, histopathological changes, urinary protein of 24 hours in rats at week 2 were measured. In situ hybridization and Western blotting were applied to measure the expression of HIF-1α and CTGF. Results At week 2, the levels of BUN, Scr and the expressions of HIF-1α and CTGF were significantly increased in UUO group compared with those in sham group (all P＜0.01). There was significant positive correlation between HIF-1α mRNA and CTGF mRNA (r＝0.697, P＜0.01). Compared with UUO group, the levels of urine protein and Scr were significantly decreased [(103.44±8.76) mg/24 h vs (278.23±26.15) mg/24 h, P＜0.01; (109.15±3.93) μmol/L vs (185.04±13.45) μmol/L P＜0.01], and renal tubulointerstitial lesion area became smaller (0.28±0.02 vs 0.51±0.05, P＜0.01) in irbesartan group. The expression of HIF-1α mRNA and protein was also significantly decreased after the treatment of irbesartan (all P＜0.01). Conclusions The expressions of HIF-1α and CTGF in UUO rats increase significantly. Irbesartan can improve renal fibrosis through down-regulating the expression of HIF-1α and CTGF.     

Skeletal muscle wasting in diabetic kidney disease rats and the effect of low-protein diet combined with ɑ-keto acids

Objective To observe the muscle wasting in diabetic kidney disease (DKD) model of type 2 and non-obese diabetes mellitus in Goto-Kakizaki (GK) rats, and to evaluate the effect of low-protein diet supplemented with ɑ-keto acids on muscle wasting. Methods Forty-five male 24-week-age GK rats were randomly divided into three groups: normal protein diet group (22% casein diet, NPD), low protein diet group (6% casein diet, LPD) and LPD＋ɑ-keto group (5% casein＋1% ɑ-keto, Keto). Fifteen gender- and age-matched Wistar rats were served as the control group (CTL). The living condition of GK rats was observed and body weight was measured once a week. Urine albumin, serum glucose, lipids, albumin, creatinine and urea nitrogen were measured at the age of 24, 32, 40, 48 weeks. Soleus muscle at the age of 48-week was observed to calculate the muscle size with software. Expressions of atrogin-1, MuRF-1 and MyoD, myogenin were examined by Q-PCR and Western blotting. Results Compared with the CTL group, NPD, LPD, Keto groups had lower body weight [(317.90±13.81), (330.38±11.96), (390.44±12.25) g vs (429.43±16.85) g, all P＜0.05], higher urine albumin [(14.36±5.52), (8.12±4.61), (5.58±3.50) mg/24 h vs (0.61±0.16) mg/24 h, all P＜0.05], higher serum creatinine [(81.50±7.88), (66.32±8.36), (63.44±8.21) μmol/L vs (24.43±6.15) μmol/L, all P＜0.05] and urea nitrogen [(7.53±1.05), (5.63±1.40), (5.54±0.97) mmol/L vs (2.98±0.62) mmol/L, all P＜0.05]. The cross-sectional area of soleus muscle fibers was larger in CTL group. Compared with CTL group, the expression levels of atrogin-1 and MuRF-1 increased significantly (all P＜0.05), and of MyoD and myogenin decreased significantly in NPD, LPD, Keto groups (all P＜0.05). In Keto group after 40 weeks, muscle wasting was improved compared with NPD and LPD group [body weight (381.62±15.82) g vs (331.50±17.58), （326.60±13.43) g, all P＜0.05], cross-sectional area of soleus muscle increased, levels of urine albumin, serum creatinine and urea nitrogen decreased (all P＜0.05), the protein expressions of atrogin-1 and MuRF-1 decreased, and myogenin and MyoD were higher as compared to CTL group (all P＜0.05). There were no significant differences between NPD and LPD group. Conclusions In DKD condition, protein degradation in the skeletal muscle is accelerated, the genes which control muscle atrophy are activated, and proliferation and differentiation of the muscle satellite cells are impaired. Low-protein diet supplemented with ɑ-keto acids can improve muscle wasting induced by DKD.     

Study of the homocysteine status in children with chronic renal failure

BACKGROUND/AIMS: Vascular diseases are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients and they cannot be explained entirely by the prevalence of traditional risk factors for atherosclerosis. The role of hyperhomocysteinemia as an additional risk factor in the development of accelerated atherosclerosis and/or thrombosis in these patients has been suggested possibly due to homocysteine (Hcy) induced endothelial cell injury. This study was aimed at evaluation of the Hcy status in children with chronic renal failure (CRF) especially in those suffering from ESRD and the possible role of folic acid and vitamin B12 therapy in the correction of hyperhomocysteinemia if present. METHODS: This study included 40 patients with CRF, 30 on regular hemodialysis (HD) treatment (group I) and 10 on conservative (medical) treatment (group II) in comparison to 20 healthy age- and sex-matched controls (group III). The basal serum levels of Hcy, folic acid and vitamin B12 as well as plasma level of activated protein C resistance (APC-R) were measured in patients and controls. RESULTS: The mean serum Hcy was significantly higher in those on regular HD (17.9 +/- 10.07 micromol/l) in comparison to those on conservative treatment (8.05 +/- 2.99 micromol/l) (p < 0.001) and controls (7.07 +/- 2.24 micromol/l) (p < 0.001), while there was no significant variation between the latter two groups. The mean values of APC-R, folic acid and vitamin B12 failed to show any significant difference in the three studied groups. No significant difference in the basal Hcy level between patients with previous history of vaso-occlusive disease and those without was found. Half of the patients on regular HD (group Ia) (n = 15) were given folic acid as 50 mg of 5-formyl-tetrahydrofolate (the active form of folic acid) intravenously once weekly after the dialysis session for 4 weeks. The other half (group Ib) (n = 15) received in addition to folic acid therapy, vitamin B12 1,000 microg hydroxycobalamine once intramuscularly. After therapy the mean Hcy decreased significantly in those who received folic acid and vitamin B12 (7.80 +/- 3.77 micromol/l) (p < 0.001) to a level comparable to the basal levels in conservative and control groups, whereas a non-significant decrease was found in those who received folic acid only (13.3 +/- 11.47 micromol/l) (p > 0.05). CONCLUSIONS: Hcy is high in children with ESRD on regular HD and combined therapy of the active form of folic acid and vitamin B12 is of value in decreasing Hcy values comparable to that in controls.     

Effects of uric acid on mitochondrial oxidative damage and apoptosis in human renal tubular epithelial cells

Objective To observe the effects of uric acid (UA) on mitochondrial oxidative damage and apoptosis in renal tubular epithelial cells (HK-2), and investigate the possible mechanism. Methods HK-2 cells were exposed to UA (480 μmol/L, 720 μmol/L) for different time (0 h, 24 h, 48 h) in vitro. The mitochondrial ROS production was detected by MitoSOX staining. The mitochondrial membrane potential was measured by JC - 1 staining. The expressions of prohibitin and AIF were examined by Western blotting and immunofluorescence cytochemistry. The cell apoptosis was measured by Annexin V-FITC/PI staining. Results The mitochondrial ROS production in HK-2 cells exposed to 480 μmol/L UA was increased than that of control group at 24 h (P﹤0.05), and increased gradually with UA concentration and incubation time increasing, while the mitochondrial membrane potential was reduced at the same time. There were no significant changes in AIF expression and apoptosis rate of HK -2 cells exposed to 480 μmol/L UA for 24 h compared with that of control group (P﹥0.05), while both of them were up-regulated when HK-2 cells were exposed to 480 μmol/L UA for 48 h and 720 μmol/L UA for 24 h and 48 h (P﹤0.05). The prohibitin expression in HK-2 cells exposed to 480 μmol/L UA was reduced than that of control group at 24 h (P ﹤ 0.05), and down - regulated gradually with UA concentration and incubation time increasing. Conclusion Uric acid can induce the mitochondrial ROS production increased, the mitochondrial membrane potential reduced, the prohibitin expression down-regulated and the mitochondrial apoptosis pathway activated in HK-2 cells.