Rhoden Ernani Luís, Rhoden Cláudia Ramos, Lucas Márcio Luís, Pereira-Lima Luiz, Zettler Cláudio, Belló-Klein Adriane
Course of Post-Graduation in Medical Clinic, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Transpl Immunol. 2002 Nov;10(4):277-84. doi: 10.1016/s0966-3274(02)00079-5.
Nitric oxide (NO), synthesized from L-arginine by the enzyme nitric oxide synthase (NOS), seems to play an ambiguous role during tissue ischemia-reperfusion injury. Our objective was to evaluate the effects of L-arginine, a NO donor, and N(G)-nitro-L-arginine-methylester (L-NAME), a NOS inhibitor, on oxidative stress, renal dysfunction, histologic alterations and surgical mortality rate induced by renal ischemia-reperfusion (RIR) in uninephrectomized rats.
One-hundred and ninety-seven Wistar rats were randomized into five experimental groups. Group 1: sham operation; group 2: right uninephrectomy (UNI); group 3: UNI + RIR in the contralateral kidney; group 4: UNI + L-NAME (20 mg/kg; intraperitoneally) + RIR; and group 5: UNI + L-arginine + RIR. The effect of the drugs was evaluated by lipid peroxidation measured by the renal malondialdehyde (MD) content and chemiluminescence (CL) levels, serum creatinine (Cr) levels, urinary volume, tubular necrosis and athrophy, inflammatory infiltrate, interstitial fibrosis as histologic evaluation and surgical mortality rate after the procedures. A P value less than 0.05 was considered significant.
Right uninephrectomy did not alter the renal parameters. RIR increased Cr levels (at 24 and 96 h of reperfusion), index of lipid peroxidation (both MD and QL levels), and worsened the histologic aspects. Pretreatment with L-arginine reduced the kidney levels of QL when compared with the non-treated group (5574 +/- 909 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) but increased the MD levels (0.97 +/- 0.24 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Moreover, L-arginine attenuated the increment of Cr levels, inflammatory infiltrate and tubular athrophy in rats subjected to RIR (P < 0.05). On the other hand, pretreatment with L-NAME increased both CL (17 482 +/- 4397 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) and MD levels (1.16 +/- 0.11 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Furthermore, L-NAME worsened the renal dysfunction (P < 0.05) at 192 h after the RIR, and surgical mortality rates were similar (P > 0.05).
L-arginine has a tendency to exert a beneficial effect on renal damage during RIR in rats. Moreover, L-NAME seems to worsen the renal damage by increasing the kidney-levels of CL and impairment of renal function probably due to reduction of NO production.
一氧化氮（NO）由一氧化氮合酶（NOS）催化L-精氨酸合成，在组织缺血再灌注损伤过程中似乎发挥着模糊不清的作用。我们的目的是评估NO供体L-精氨酸和NOS抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）对单侧肾切除大鼠肾缺血再灌注（RIR）诱导的氧化应激、肾功能障碍、组织学改变及手术死亡率的影响。
197只Wistar大鼠随机分为5个实验组。第1组：假手术；第2组：右侧单侧肾切除（UNI）；第3组：对侧肾脏UNI + RIR；第4组：UNI + L-NAME（20mg/kg；腹腔注射）+ RIR；第5组：UNI + L-精氨酸 + RIR。通过测定肾丙二醛（MD）含量和化学发光（CL）水平评估脂质过氧化、血清肌酐（Cr）水平、尿量、肾小管坏死和萎缩、炎症浸润、间质纤维化等组织学指标以及手术后的手术死亡率来评价药物的作用。P值小于0.05被认为具有统计学意义。
右侧单侧肾切除未改变肾脏参数。RIR使Cr水平升高（再灌注24小时和96小时）、脂质过氧化指标（MD和CL水平）增加，并使组织学情况恶化。与未治疗组相比，L-精氨酸预处理降低了肾脏CL水平（5574±909 vs. 13660±1104 cps/mg蛋白；P < 0.05），但增加了MD水平（0.97±0.24 vs. 0.79±0.06 nmol/mg蛋白；P < 0.05）。此外，L-精氨酸减轻了RIR大鼠Cr水平的升高、炎症浸润和肾小管萎缩（P < 0.05）。另一方面，L-NAME预处理增加了CL（17482±4397 vs. 13660±1104 cps/mg蛋白；P < 0.05）和MD水平（1.16±0.11 vs. 0.79±0.06 nmol/mg蛋白；P < 0.05）。此外，L-NAME在RIR后192小时使肾功能障碍加重（P < 0.05），手术死亡率相似（P > 0.05）。
L-精氨酸对大鼠RIR期间的肾损伤有发挥有益作用的趋势。此外，L-NAME似乎通过增加肾脏CL水平和可能由于NO生成减少导致的肾功能损害而加重肾损伤。
