AngⅡ拮抗剂对慢性肾衰大鼠肾血流量和肾内氧耗的影响

摘要

目的：观察血管紧张素II（ AngⅡ）拮抗剂对5/6（ ablation /infarction，A/I）肾切除诱导慢性肾衰竭（ CRF）大鼠肾功能、肾血流量及肾内氧耗的影响。方法制备5/6（ A/I）肾切除诱导慢性肾衰大鼠模型，设正常组（ A组，n ＝14只），模型组（ B组，n ＝14只），AngⅡ拮抗剂治疗组（氯沙坦钾联合福辛普利钠）（ C组，n ＝14只）。给予相应干预，疗程60 d。分别测量尾动脉收缩压（ SBP）、舒张压（ DBP），检测大鼠尾静脉血清肌酐（ Scr）、尿素氮（ BUN）、血红蛋白（ Hb），计算内生肌酐清除率（ Ccr）。干预60 d后，检测肾血流量（ RBF）、腹主动脉和肾静脉血气（AABG and RVBG），左肾静脉压（RVpO2），计算残余肾内氧耗（ QO2/TNa）及观察残肾组织病理变化。结果（1）造模后与A组比较，B、C两组的Scr、BUN和尾动脉SBP、DBP显著增加（P＜0.01），Ccr、Hb显著降低（P＜0.01），提示造模成功。（2）干预后与B组比较，C组的Scr、尾动脉SBP、DBP、QO2/TNa明显下降（P＜0.01），BUN降低（P＜0.05），Hb、Ccr、RVpO2显著升高（P＜0.01），RBF升高（P＜0.05）。（3）残肾组织病理形态学变化显示，C组的肾组织病理变化明显减轻，优于B组。结论 AngⅡ拮抗剂可以增加慢性肾衰大鼠肾血流量，降低肾内氧耗，改善肾功能及减轻肾组织病理变化，其肾脏保护作用机制可能与其调节细胞能量代谢，改善肾内氧耗有关。%Objective To observe the effects of angiotensin Ⅱ( Ang Ⅱ) blockade on renal function, renal blood flow and renal oxygen consumption in chronic renal failure ( CRF) rats induced by 5/6th kidney ablation /infarction (5/6A/I).Methods Sprague-Dawley rats were randomly divided into 3 groups:the normal group (group A, n =14), mod-el group (group B, n=14) and angiotensin II blockade (Cozaar with Monopril) treatment group (group C, n =14).The chronic renal failure ( CRF) rat models were induced by 5/6th kidney ablation/infarction.The tail artery systolic pressure (SBP), diastolic blood pressure (DBP) and tail vein serum creatinine (Scr), blood urea nitrogen (BUN), hemoglobin ( Hb) and creatinine clearance rate ( Ccr) were assessed before and after intervention.The course of treatment was sixty days.The renal blood flow ( RBF) , blood gas analysis of abdominal aortic and renal vein, left renal vein pressure ( RV-pO2 ) were detected and remnant renal oxygen consumption ( QO2/TNa ) was calculated, and the pathological changes of remnant kidney were observed after the 60 d intervention.Results (1) Compared with the group A, the levels of Scr, BUN and tail artery SBP, DBP were significantly increased ( P<0.01 for all) , and the levels of Ccr and Hb were signifi-cantly decreased ( P<0.01) in the groups B and C, demonstrating the successful modeling.(2) Compared with the group B, the levels of Scr, tail artery SBP, DBP and QO2/TNa were significantly decreased (P<0.01 for all), the levels of BUN were decreased (P<0.05), the levels of Hb, Ccr and RVpO2 were significantly increased (P<0.01 for all), the level of RBF was increased ( P<0.05) in the group C after intervention.(3) The histopathological examination of the remnant re-nal tissue showed that the pathological changes in the group C were apparently reduced, better than those of the Group B. Conclusions Angiotensin II blockade can increase RBF, reduce renal oxygen consumption, improve renal function, and reduce the renal pathological changes in CRF rats.The mechanism of renal protection may be related to the regulation of cellular energy metabolism and improvement of renal oxygen consumption.