环孢霉素A对肾性高血压大鼠重要脏器钙调神经磷酸酶活性的调控

背景近来大量研究表明,钙调神经磷酸酶依赖的信号转导通路在免疫系统、神经系统、心血管系统具有广泛的生物学效应,钙调神经磷酸酶活性改变与多种疾病发生发展密切相关.目的通过建立一肾一夹肾性高血压大鼠模型,观察高血压大鼠心脏、脾、肾脏、肺、脑、肝、主动脉等重要组织脏器钙调神经磷酸酶活性变化及环孢霉素A的调控作用.设计完全随机分组设计,对照实验.单位解放军总医院南四科.方法实验于2002-11/2003-06在解放军总医院老年外科实验室完成.选用雄性Wistar大鼠(清洁级)20只.动物随机分为3组肾性高血压组n=7,行一肾一夹手术,术后第4天开始给予生理盐水1 mL/(kg·d)腹腔注射,9 g/L盐水代饮水至4周],环孢霉素A干预组(n=7,行一肾一夹手术后第4天给予环孢霉素A 5 mg/(kg·d)腹腔注射,9 g/L盐水代饮水至4周),假手术组(n=6,除不切除右肾及狭窄左肾动脉外,其余操作同手术组,假手术后第4天开始给予生理盐水1 mL/(kg·d)腹腔注射,正常饮水至4周).一肾一夹模型制作方法将大鼠腹腔注射麻醉后,行右肾切除,左肾用直径0.2 mm银夹狭窄左肾动脉.采用tail-cuff测压法测鼠尾收缩压.以对硝基磷酸酚为底物测定术后4周大鼠各组织器官钙调神经磷酸酶活性.两组差异性比较采用成组资料t检验.主要观察指标①各组大鼠各重要组织及器官钙调神经磷酸酶活性比较.②各组大鼠术前及术后4周收缩压比较.结果大鼠20只均进入结果分析.①收缩压术前三组大鼠相近(P＞0.05).术后4周环孢霉素A干预组低于肾性高血压组,但差异不明显;肾性高血压组和环孢霉素A干预组大鼠均明显高于假手术组(t=2.54,3.01,P＜0.05).②肾、肺、心、脾、脑组织钙调神经磷酸酶活性肾性高血压组大鼠明显高于假手术组(t=3.17～7.08,P＜0.05),环孢霉素A干预组明显低于肾性高血压组(t=2.91～7.25,P＜0.05).③肝细胞钙调神经磷酸酶活性肾性高血压组和环孢霉素A干预组均明显低于假手术组(t=2.63,2.83,P＜0.05).④主动脉钙调神经磷酸酶活性各组大鼠相近.结论①肾性高血压大鼠心、脑、肾脏、脾脏、肺脏组织钙调神经磷酸酶活性均有显著升高,环孢霉素A对肾性高血压大鼠上诉各组织脏器钙凋神经磷酸酶活性具有广泛的抑制作用.②环孢霉素A无明显降肾性高血压大鼠收缩压作用.

Study of the alteration of calcineurin activity regulated by cyclosporine A in vital organs of 1K1C renal hypertensive rats

BACKGROUND: Recently massive studies have indicated that calcineurin (CaN) dependent signal transduction pathway exerts widespread biological effects in the immune system, neural system and cardiovascular system, moreover CaN activity is closely associated with the onset and development of various diseases.OBJECTIVE: To establish the one-kidney and one-clip renal hypertensive rat model, to observe the alternation of CaN activity in the vital organs,such as heart, spleen, kidney, lung, brain, liver, aorta and so on, and to investigate the regulating function of Cyclosporine A(CsA) on CaN activity.DESIGN:Completely randomized controlled experiment.SETTING: South Fourth Department of General Hospital of Chinese PLA.METHODS: This experiment was carried out at the aging surgical department laboratory of the General Hospital of Chinese PLA from November 2002 to June 2003. Totally 20 male Wistar rats (clean grade) were randomly divided into three groups: namely renal hypertension group n=7,rats were subjected to 1K1C operation and given intraperitoneal injection 4 days, drinking water replaced by 9 g/L salt water until postoperative 4weeks ], cyclosporine A intervention group (n=7, rats were subjected to the same management as renal hypertension group except for physiological operation group (n=6, rats receive the same operation as operation group except for not excising the right kidney and narrowing left kidney artery,and rats were given intraperitoneal injection of physiological saline by ter replaced by 9 g/L salt water until postoperative 4 weeks and drinking water until postoperative 4 weeks). 1K1C model establishment method: After anesthetized by intraperitoneal injection, rats were subjected to right kidney excision with left kidney artery narrowed by 0.2 mm silver clamp.Tail-cuff manometry was used to detect systolic pressure at rat-tail. Meanwhile, nitro phosphoric acid phenol was taken as substrate to determine the CaN activity in rat vital organs at postoperative 4 weeks. Using t-test compared difference between two groups.tween pre-operation and postoperative 4 weeks in each group.RESULTS: Totally 20 rats were enrolled in this study and all data was three groups before operation (P ＞ 0.05). And at postoperative week 4,cyclosporine A group showed lower systolic pressure than that of renal hypertension group, but the difference was not remarkable; it was significantly higher in both renal hypertension group and cyclosporine A intervention group comparing to sham operation group (t=2.54,3.01, P ＜ 0.05).group showed obviously higher CaN activity than that of sham operation group (t=3.17-7.08, P ＜ 0.05), and the CaN activity in cyclosporine A group was obviously lower than that of renal hypertension group (t=2.91-7.25,hypertension group and cyclosporine A intervention group than that of almost the same in all groups.heart, brain, kidney, spleen and lung of renal hypertensive rats, which can pressive effect on systolic pressure in renal hypertensive rats.