慢性运动和抗高血压治疗对慢性肾衰竭高血压大鼠的肾脏保护作用。

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure.

作者信息

Kohzuki M, Kamimoto M, Wu X M, Xu H L, Kawamura T, Mori N, Nagasaka M, Kurosawa H, Minami N, Kanazawa M, Saito T, Yoshida K

机构信息

Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

J Hypertens. 2001 Oct;19(10):1877-82. doi: 10.1097/00004872-200110000-00024.

DOI:10.1097/00004872-200110000-00024

PMID:11593110

Abstract

OBJECTIVES

Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function.

DESIGN AND METHODS

Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks.

RESULTS

Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in the model as a significant predictors of mean proteinuria (weeks 1-4) (all P < 0.0001).

CONCLUSIONS

These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

摘要

目的

慢性肾衰竭患者的身体活动受限，往往缺乏运动。然而，关于长期运动对肾病进展的影响的报道很少。同样，涉及运动训练对改善肾功能影响的动物模型也很少。因此，我们评估了中度慢性跑步机运动对自发性高血压大鼠（SHR）慢性肾衰竭残余肾模型的肾脏影响。我们还评估了运动和抗高血压治疗对肾功能的影响。

设计与方法

8周龄的SHR通过切除左肾和切除右肾的三分之二进行5/6肾切除术。大鼠分为四组：（i）不运动（非运动组）；（ii）中度跑步机运动（20米/分钟，0度坡度，60分钟）（运动组）；（iii）运动组联合血管紧张素转换酶（ACE）抑制剂依那普利（每天2毫克/千克，腹腔注射）；（iv）运动组联合血管紧张素受体拮抗剂氯沙坦（每天5毫克/千克，腹腔注射），持续4周。

结果

长期运动显著减轻蛋白尿增加（P < 0.01），并显著防止肾小球硬化指数（IGS）增加。依那普利和氯沙坦与运动联合使用均显著降低血压（P < 0.001），并进一步降低IGS。在逐步多元回归分析中，只有抗高血压药物作为IGS的显著预测因子保留在模型中（P < 0.0001）。相比之下，运动、抗高血压药物和平均收缩压（第1 - 4周）作为平均蛋白尿（第1 - 4周）的显著预测因子保留在模型中（所有P < 0.0001）。