曲尼司特对环孢素A诱导的人肾小管上皮细胞向间充质转变的抑制作用

目的 研究曲尼司特(Tran)对环孢素A(CsA)诱导的人肾小管上皮细胞(HK-2)向间充质转变的影响,并探讨该药抗纤维化的机制.方法 所有用于实验的HK-2细胞株均为8～12代细胞,分为4组:(1)空白对照组,收获细胞,不做任何处理;(2)CsA组,加入4.2μmol/LCsA;(3)CsA+Tran组,预先加入100μmol/L Tran,作用2 h后再加入4.2 μmol/L CsA;(4)Tran组,仅加入100μmol/L Tran.72 h后于共聚焦显微镜下观察各组细胞形态学变化;用免疫荧光法以及免疫印迹法检测各组钙黏蛋白(E-cadherin)、平滑肌肌动蛋白α(α-SMA)和骨桥蛋白(OPN)的表达.结果 HK-2细胞在正常情况下表现为典型的"鹅卵石"样形态,细胞圆钝,且与邻近的细胞连接较为紧密;空白对照组和Tran组细胞表现为典型的HK-2细胞形态;CsA组细胞变狭长,甚至向周边伸出"伪足"样改变,细胞间连接较为稀疏;CsA+Tran组的细胞形态学改变有明显改善.CsA组细胞E-cadherin荧光表达强度明显弱于对照组,α-SMA、OPN荧光表达强于对照组;CsA+Tran组细胞E-cadherin荧光表达强于CsA组,α-SMA、OPN荧光表达弱于CsA组.免疫印迹检查中,CsA组细胞E-cadherin 的表达明显低于对照组,而α-SMA、OPN的表达明显高于对照组,CsA+Tran组细胞E-cadherin的表达高于CsA组,而α-SMA、OPN的表达低于CsA组.结论 曲尼司特能抑制CsA诱导的HK-2细胞由肾小管上皮向间充质细胞转化的过程,其机制可能与抑制OPN的表达有关.

Abstract：

Objective To study the effect of tranilast on cyclosporine A (CsA)-induced epithelial-to-mesenchymal transition in human renal tubular epithelial cells, and investigate the mechanism of its antifibrotic effect. Methods Cultured HK-2 cells were divided into four groups: (1)In the control group, cells were treated without any medicine; (2) The cell were treated with CsA (4. 2μmol/L) for 72 h; (3) The cells were treated with a combination of CsA (4. 2 μmol/L) and tranilast (100μmol/L); (4) The cells were treated with tranilast (100 μmol/L) alone for 72 h.Morphological changes of the cells were assessed by phase-contrast microscopy. The immunofluorescence and Western blotting were adopted to detect the expression of E-cadherin, α-SMA and OPN mRNA and proteins respectively. Results Tranilast could markedly ameliorate the morphological changes of HK-2 cells stimulated by CsA. The irmmunofluorescence staining revealed the expression of E-cadherin was markedly decreased in HK-2 cells stimulated with CsA for 72 as compared with the control group, while the expression of α-SMA and OPN was significantly higher in CsA group than the control group. The expression of E-cadherin in the CsA + Tranilast group was higher than the CsA group, while the expression of α-SMA and OPN in the CsA + Tranilast group was lower than the CsA group. Western blotting showed that protein expression level of E-cadherin in CsA group was dramatically lower than that in the control group (P＜0. 05), while that of α-SMA and OPN in CsA group was significantly higher than in the control group (P＜0.05). The protein expression level of E-cadherin in HK-2 cells in the CsA + Tranilast group was markedly higher than in the CsA group (P＜0.05), and that of α-SMA and OPN in CsA + Tranilast group was significantly lower than in the CsA group (P＜0. 05). Conclusion Tranilast can block the CsA-induced epithelialto-mesenchymal transition in HK-2 cells probably by suppressing the expression of OPN.     

曲尼司特对环孢素A诱导的人肾小管上皮细胞向间充质转变的抑制作用

Objective To study the effect of tranilast on cyclosporine A (CsA)-induced epithelial-to-mesenchymal transition in human renal tubular epithelial cells, and investigate the mechanism of its antifibrotic effect. Methods Cultured HK-2 cells were divided into four groups: (1)In the control group, cells were treated without any medicine; (2) The cell were treated with CsA (4. 2μmol/L) for 72 h; (3) The cells were treated with a combination of CsA (4. 2 μmol/L) and tranilast (100μmol/L); (4) The cells were treated with tranilast (100 μmol/L) alone for 72 h.Morphological changes of the cells were assessed by phase-contrast microscopy. The immunofluorescence and Western blotting were adopted to detect the expression of E-cadherin, α-SMA and OPN mRNA and proteins respectively. Results Tranilast could markedly ameliorate the morphological changes of HK-2 cells stimulated by CsA. The irmmunofluorescence staining revealed the expression of E-cadherin was markedly decreased in HK-2 cells stimulated with CsA for 72 as compared with the control group, while the expression of α-SMA and OPN was significantly higher in CsA group than the control group. The expression of E-cadherin in the CsA + Tranilast group was higher than the CsA group, while the expression of α-SMA and OPN in the CsA + Tranilast group was lower than the CsA group. Western blotting showed that protein expression level of E-cadherin in CsA group was dramatically lower than that in the control group (P＜0. 05), while that of α-SMA and OPN in CsA group was significantly higher than in the control group (P＜0.05). The protein expression level of E-cadherin in HK-2 cells in the CsA + Tranilast group was markedly higher than in the CsA group (P＜0.05), and that of α-SMA and OPN in CsA + Tranilast group was significantly lower than in the CsA group (P＜0. 05). Conclusion Tranilast can block the CsA-induced epithelialto-mesenchymal transition in HK-2 cells probably by suppressing the expression of OPN.     

The Antiandrogen Withdrawal Syndrome

Objective To evaluate the response to antiandrogen withdrawal in patients with advanced prostate cancer treated with combined androgen blockade.Methods Twenty-four cases of advanced prostate cancer (10in stage C and 14 in stage D) were retrospectively studied.All the patients were treated with combined androgen blockade(bilateral orchiectomy and flutamide).After initial response to hormone therapy for 7 to 36 months,flutamide was discontinued because of deterioration of the disease.Serum prostate specific antigen(PSA) levels were checked every 2 to 4 weeks and symptoms observed.Results The results following withdrawal of flutamide were as follows:8 patients showed a decling in PSA(mean 74.8%),of whom 6 cases had the PSA decling greater than 50%.Clinical symptoms improved in 4 cases.The nodules of the prostate were smaller than before in cases.The mean duration of response was 4.3 months.Conclusion In patients with hormone refractory advanced prostate cancer after initial combined androgen blockade therapy,a trial of “antiandrogen withdrawal”is a reasonable choice of therapeutic maneuver.     

腹腔镜活体供肾切取术10例报告

目的　探讨活体供肾切取新方法。方法　对 10名亲属活体供肾者采用腹腔镜切取供肾 ,供者采用全身麻醉 ,经腹腔途径 ,取右侧卧位 ,在脐旁、剑突下偏右及左腹股沟韧带中点上方1.5cm各开一孔 ,脐旁放入观察镜 ,另两孔为操作孔。供肾经左下腹操作孔的延长切口用手取出。供、受者术后随访 2～ 12个月。结果　供肾切取耗时 (3.6± 0 .6 )h ,热缺血时间平均 4 .5min ;供者术后无并发症发生 ,肾功能正常 ,住院时间 (5± 1)d ,术后 2个月内均恢复正常工作。结论　腹腔镜活体供肾切取术是一种创伤小的供肾切取方法 ,供者术后疼痛轻 ,恢复快。     

肾自体移植术治疗肾动脉狭窄性高血压——(附2例报告)

肾动脉狭窄性高血压,约占高血压病的 5-20％①,由于可以通过外科手术治疗,近来已引起临床医师重视。肾动脉狭窄的原因有:(1)大动脉炎,(2)肾动脉粥样硬化,(3)肾动脉中膜层纤维肌增殖,(4)先天性肾动脉畸形,(5)肾下垂扭转牵拉肾蒂血管,(6)肾动脉及其分枝的血栓或栓塞等。在我国以大动脉炎为较常见。其病变往往发生在腹主动脉,引起缩窄性腹主动脉炎,同时可累及一侧或双侧肾动脉,造成不同程度的狭窄。     

双J支架管在肾移植手术中的应用

肾移植术后出现尿瘘或吻合口狭窄、梗阻是移植后严重的手术并发症，尽管肾移植的外科技术逐渐提高，但仍偶有发生。随着腔道泌尿外科的发展及泌尿道内引流支架管制作材料的不断改进，利用特殊类型的双Ｊ管作为肾移植术后的内引流支架，可减少和预防肾移植术后尿路并发症。...     

体外冲击波碎石治疗上尿路结石240例分析

报告1989年3月至1990年3月应用与中国科学院联合研制的KDE-Ⅱ型体外冲击波碎石机治疗240例上尿路结石病人。总碎石率为99.58％,三个月内的排石率为89.70％。对并发症及其顶防进行了探索性讨论,提出预防或减少并发症的方法。     

甲状旁腺全切加前臂移植术治疗肾衰继发重症甲状旁腺功能亢进(附九例报告)

目的　探讨甲状旁腺全切加前臂移植术治疗肾衰继发重症甲状旁腺功能亢进 (SHP)的临床疗效。　方法　回顾性分析 9例患者资料 ,从定位诊断、手术适应证、围手术期处理等方面进行讨论。　结果　 9例患者共切除增生甲状旁腺 35枚 ,单人总量 2 .3～ 7.8g ,1例加行左甲状腺切除。移植腺体均成活 ,移植侧上肢PTH与对侧之比 >1.5 ,临床症状改善 ,各项化验结果逐步恢复正常。　结论　对内科治疗无效的肾衰继发重症甲状旁腺功能亢进 ,甲状旁腺全切加前臂移植是一种安全、有效的治疗方法。     

难拔气囊导尿管的处理体会

难拔气囊导尿管的处理体会华立新徐正铨程双管（南京医科大学第一附属医院泌尿外科，南京２１００２９）关键词导尿管；气囊；拔管气囊导尿管在临床有着广泛的应用，但在临床实践中，亦不时遇到导尿管难拔的情况。本文结合典型病例，讨论有关处理方法。１典型病例例１男，...     

原发性附睾腺癌一例报告

患者　 5 7岁。因右睾丸肿胀、坠痛40ｄ于 2 0 0 0年 4月 5日入院。曾以附睾炎处理 ,无效 ,肿块渐增大 ,且疼痛加剧。查体 :右附睾肿大 ,尾部可及一肿块约2ｃｍ× 2ｃｍ× 1ｃｍ ,质硬 ,触痛明显 ,结节感 ,与阴囊皮肤无粘连。右侧精索增粗。双腹股沟区未扪及明显肿大淋巴结。直肠指检 :前列腺Ⅱ度增生 ,质中等 ,中央沟变浅 ,两侧叶未扪及结节。Ｂ超检查 :右侧睾丸后下方及上极见低回声区 ,肿瘤待排。诊断 :右侧附睾占位病变 ,肿瘤待排除。给予抗感染治疗 1周 ,症状体征未改善。血清甲胎蛋白 (ＡＦＰ)和绒毛膜促性腺激素 (β ＨＣＧ)正常 ,血…