【作者】 吴昊；

【导师】 洪小苏；

【作者基本信息】 苏州大学 ， 心血管内科， 2002， 硕士

【摘要】 目的 探讨不同降压药物对1月龄自发性高血压大鼠(spontaneously hypertensive rat，SHR)肾脏细胞增生与凋亡的影响并评价其意义。 方法 选择1月龄SHR 36只(雄24只，雌12只)作为受试对象，按随机区组设计分为六组，用五种不同降压药包括普萘洛尔(50mg／kg／d)、硝苯地平(35mg／kg／d)、依那普利(30mg／kg／d)、氢氯噻嗪(75mg／kg／d)和缬沙坦(30mg／kg／d)进行干预并设对照组，按照常用降压剂量灌胃六周后，剖腹取双肾，用末端脱氧核糖核酸转移酶介导的带荧光的dUTP缺口末端标记法(TUNEL)标测肾脏凋亡细胞和用透射电子显微镜观察凋亡细胞超微结构，分别检测不同降压药物对1月龄SHR肾脏重量指数和细胞凋亡指数的影响及其规律。 结果 1．依那普利组(6.52±0.32 mg／g)和缬沙坦组(6.39±0.27mg／g)分别与对照组(7.25±0.22mg／g)比较，肾脏重量指数明显下降(P＜0.01)；硝苯地平组(6.73±0.21 mg／g)与对照组比较，肾脏重量指数下降(P＜0.05)；普萘洛尔组(7.09±0.32 mg／g)和氢氯噻嗪组(7.22±0.53 mg／g)分别与对照组比较，肾脏重量指数差别无统计意义(P＞0.05)。 2．普萘洛尔组(49.20±5.17％)、依那普利组(56.47±.9.08％)、硝苯地平组(51.08±9.59％)和缬沙坦组(55.73±4.34％)分别与对照组(35.19±4.05％)比较，肾脏细胞凋亡指数明显升高(P＜0.01)；氢氯噻嗪组(37.23±1.95％)与对照组比较，肾脏细胞凋亡指数差别无统计意义(P＞0.05)。 3．依那普利组(35.13±8.73％)、硝苯地平组(35.80±11.03％)和缬沙坦组(34.20±4.26％)分别与对照组(19.13±1.86％)比较肾小球细胞凋亡指数升高(P＜0.01)；普萘洛尔组(27.13±3.20％)和氢氯噻嗪组(19.80±1.96％)与对照组比较，肾小球细胞凋亡指数差别 阵K药物对未成年【’］人们；高血＊大鼠肾脏细胞增Q。与凋广＿的影响及其意义 摘要 无统计意义叮功．05）【4．普蔡洛尔组（1．88f3．57％）、依那普禾组（1．33t3．44％）和‘濒沙坦组Q．53到．86％）分别与对照组门．07H．48O／O）比较，肾小 管细胞凋亡指数升高呼叩．of）；硝苯地平组（l．28L2．03o／o）和氢 氯暖喷组门 17．35fi．83％）比较，肾小管细胞凋亡指数差别无统计意 义（P＞0．05） 5．肾脏细胞凋亡指数与肾脏重量指数呈明显负相关h—0．496， P＜0．们） 6．肾脏凋亡细胞超微结构观察：肾脏细胞胞质变深（胞质浓缩） 和胞核染色质浓缩边聚（核固缩） 结论 1．未成年SHR（血压升高之前）肾脏重量指数明显增加， 这种改变与肾脏细胞凋亡指数呈显著负相关，提示存在肾脏细胞增生 与凋亡的不平衡状态。 2．部分种类的降压药物（依那普利、颧沙坦、硝苯地平和普蔡洛 尔）干预，可改善未成年肛 I肾脏细胞增生和凋亡之间的失衡状态， 且这种作用是非血压依赖的，提示早期于预对SHR肾脏保护司能具 有重要的价值。 3．噎噎类利尿剂早期十预对未成年 SHR肾脏无保护作用。 4．肾肌细胞重量指数和细胞凋亡指数可以作为评价降压药物作 用和观察肾赃组织重塑的重要指标。更多还原

【Abstract】 Objective To investigate the effects of renal cell hyperplasia and apoptosis about treatment with various antihypertensive drugs on one-month-old spontaneously hypertensives rats (SHRs) and evaluate its significance.Methods 36 one-month-old SHRs (male,24;female,12) were used in the study and randomly divided into six groups,five of which were respectively handled with Propranolol (50 mg/kg/d),Nefidipine (35 mg/kg/d),Hnalapril (30 mg/kg/d),Hydrochlorothiazide (75 mg/kg/d),Valsatan (30 mg/kg/d),and the sixth group was untreated (control group). After all SHRs were received their respective treatment daily,by gastric gavage for six weeks,laparotomy was performed and the kidneys were removed. Renal cell apoptosis was then assessed by in situ dUTP biotin nick-end labeling method (TUNEL) and transmission electron microscope. We investigated the effects and dynamic changes of renal cell apoptotic indexes and renal ponderal indexes about treatment with various anti-hypertensive drugs on one-month-old SHRs.Results 1 . Renal ponderal indexes in Enalapril group (6.52+0.32 mg/g) and Valsatan group (6.39+0.27 mg/g) compared with control group (7.25+0.22 mg/g) decreased,respectively,(P<0.01). Renal ponderal indexes in Nefidipine group (6.73+0.21 mg/g) compared w7ith control group decrease (P<0.05). There was no statistical significance in renalponderal indexes in Propranolol group (7.09+0.32 mg/g) and Hydrochlorothiazide group (7.22+0.53 mg/g) compared with control group (P>0. 05).2. Renal apoptotic indexes in Propranolol group (49.02+5.1 7%),Enalapril group (56.47+9.08%),Nefidipine (51.08+9.59%) and Valsatan group (55.73+4.34%) compared with control group (35.19+4.05%) increased,respectively,(P<0.01). There was no statistical significance in renal apoptotic indexes in Hydrochlorothiazide group (37.23+ 1.95%) compared with control group (P>0.05).3. Glomerular apoptotic indexes in Enalapril group (35.13+8.73%),Nefidipine group (35.80+1 1.03%) and Valsatan group (34.20+4.26%) compared with control group (19. 13+1 .86%) increased, respectively,(P<0.01). There was no statistical significance in glomerular apoptotic indexes in Propranolol group (27.1 3+3.20%) and Hydrochlorothiazide group ( 1 9.80 +1 .96%) compared with control group (P>0.05).4. Renal tubular apoptotic indexes in Propranolol (21.88 + 3.57%),Enalapril group (21.33 +3.44%) and Valsatan group (21.53+1.86%) compared with control group (15.07 +2.48%) increased,respectively,(P<0.01). There was no statistical significance in renal tubular apoptotic indexes in Nefidipine group ( 15.28+2.03%) and Hydrochlorothiazide group ( 1 7.35 d. } .83%) compared with control group (P>0.05).5. There was a negative correlation between renal apoptotic indexes and renal ponderal indexes in juvenile SHRs (r=-0.496,P<0.01).6. The ultramicrostructural changes of renal cell apoptosis include cytoplasm compaction and segregation of nuclear chromatin into small sharply delineated electron dense masses that abut the nuclear envelope.Conclusion 1. Renal ponderal indexes of juvenile SHRs increase obviously before SHRs suffer from high blood pressure. There is asignificantly negative correlation between renal ponderal indexes and renal cell apoptotic indexes,which suggests that there is an imbalance between renal cell hyperplasia and apoptosis.2. Some kinds of antihypertensive drugs,for example,Enalapril,Valsatan,Netidipine and Propranolol,can improve the imbalance between renal cell hyperplasia and apoptosis in juvenile SHRs. The role is hypertension-independent. There may be an important value on protecting renal function because of early medication.3. Early medication of thiazidc diuretics can’t protect renal function in juvenile SHRs.4. Renal ponderal indexes and apoptotic indexes can be considered as an important mark to evaluate the role of antihypertensive drugs and to observe the process of remodeling in renal tissue.更多还原