瘦素保护脓毒症后肾功能及其机制的研究

Leptin protects sepsis-induced renal injury and research for its mechanism

目的观察脓毒症对肾功能及相关酶活性的影响,探讨瘦素(Leptin)在急性炎症反应中的作用。方法采用盲肠结扎穿孔术制备小鼠脓毒症模型,用分光光度法检测血尿酸(UA)以及肾组织匀浆液中髓过氧化物酶(MPO)、谷胱甘肽S转移酶(GST)、黄嘌呤氧化酶(XOD)、超氧化物歧化酶(SOD)等4种与自由基合成、解毒和嘌呤生成代谢相关的酶活性;采用放射免疫分析法测定肾组织匀浆液中Leptin水平,同时观察肾组织病理学改变。结果腹腔内注射Leptin(0.08mg/kg)和消炎痛(8mg/kg)可分别降低脓毒症后12h时血清UA水平〔分别为(295.79±80.86)μmol/L和(281.78±46.35)μmol/L,脓毒症组为(474.03±75.22)μmol/L〕;Leptin保护组脓毒症后12h和消炎痛保护组脓毒症后6h肾组织Leptin水平〔分别为(196.00±134.30)μg/g和(169.30±132.00)μg/g〕亦显著高于脓毒症组〔(61.65±27.29)μg/g〕。而Leptin和消炎痛保护后6h和12h对肾组织MPO、GST、XOD和SOD等酶活性有不同程度的影响,但结果并非完全抑制或促进。从总体上分析,Leptin和消炎痛有促进氧自由基清除和灭活的功能。结论低剂量Leptin可能对脓毒症后肾功能有一定的改善作用,其机制可能同消炎痛相似,与清除和灭活肾组织中氧自由基有关。

objective To detect the effect of sepsis on renal function and corresponding enzymes in mice, and to explore the role of leptin in acute inflammation. Methods Sepsis was reproduced by cecum ligation and puncture in mice. Serum uric acid （UA） and four enzymes related with synthesis of free radicals in kidney homogenized fluids, myeloperoxidase （MPO）, glutathin -S transferase （GST）, xanthine oxidase （XOD） and superoxide dismutase （SOD） were determined with spectrophotometry, and leptin level in kidney was detected by radioimmunoassay. Histopathologic changes in kidney were observed with hematoxylin-eosin staining. Results Twelve hours after leptin （0.08 mg/kg, i. p. ） and indomethacin （8 mg/kg, i.p. ） injection, serum UA was significantly decreased [（295.79±80. 86） μmol/L and （281.78±46.35）μmol/L, respectively, vs. sepsis group （474.03±75.22）μmol/L）. At the same time, renal leptin levels in leptin injection group [（196.00±134.30）μg/g） 12 hours after sepsis and in indomethacin injection group [（169.30±132.00）μg/g） 6 hours after sepsis were also significantly higher than sepsis group [（61.65±7.29）μg/g）. Six and 12 hours after leptin and indomethacin injection, renal MPO, GST, XOD and SOD activities were affected to certain extent, as the results were not completely inhibited or enhanced. Nevertheless, leptin and indomethacin could promote scavenge and deactivation of free radicals. Conclusion Low dose leptin can ameliorate sepsis-induced renal injury, which may be related with scavenge and deactivation of free radicals in renal cells, and this mechanism is similar with that of indomethacin.