目的 探讨左卡尼汀对大鼠横纹肌溶解急性肾损伤的保护作用及其作用机制。方法 48只大鼠,随机分为空白组、模型组、盐水治疗组及左卡尼汀治疗组。肌内注射50%甘油建立横纹肌溶解急性肾损伤模型,盐水治疗组、左卡尼汀治疗组分别腹腔注射生理盐水和左卡尼汀。测血清肌酸激酶(creatine kinase,CK)、尿素氮(urea nitrogen,BUN)和肌酐(serum creatinine,Scr)水平,光镜下观察肾脏病理;RT-PCR和免疫组化分别检测肾脏TLR4、NF-kB;酶联免疫吸附法检测肾脏IL-6、TNF-α。结果 与空白组相比,模型组及盐水治疗组CK、BUN、Scr、TLR4、NF-kB、IL-6、TNF-α及急性肾小管坏死(acute tubular necrosis,ATN)评分均明显升高(F=9.12~211.77,q=5.40~20.3,P<0.05);与模型组相比,左卡尼汀治疗组CK、BUN、Scr、TLR4、NF-kB、IL-6、TNF-α及ATN评分水平明显降低(q=4.37~16.03,P<0.05)。结论 左卡尼汀缓解横纹肌溶解急性肾损伤的机制可能与其抗免疫炎性反应通路TLR4/NF-kB有关。
Abstract
Objective To observe the renal function and the effect of L-carnitine on rhabdomyolysis-induced acute kidney injury(AKI) in rats.Methods Forty-eight adult rats were randomly divided into control group,model group, normal saline treatment group,and L-carnitine treatment group.50% glycerol was intramuscularly injected into double hind limbs of rats to prepare the rhabdomyolysis-induced AKI model.Normal saline treatment group and L-carnitine treatment group were intraperitoneally injected with saline and L-carnitine.An automatic biochemical analyzer was used to test levels of serum creatine kinase(CK),urea nitrogen(BUN) and creatinine(Scr) whileRT-PCR method and immunohistochemical method were employed respectively to detect the expression of TLR4、NF-kB in the kidney. Biotin method of enzyme linked immunosorbent assay(ELISA) was used to detect the expression of IL-6 and TNF-α in the kidney.Results In model group, levels of CK、BUN、Scr、TLR4、NF-kB、IL-6 and TNF-α were significantly elevated compared with control group(F=9.12-211.77,q=5.40-20.3, P<0.05).Compared with model group, levels of CK,BUN,Scr,TLR4,NF-kB,IL-6 and TNF-α were reduced significantly in L-carnitine group(q=4.37-16.03,P<0.05).Conclusions L-carnitine can ameliorate rhabdomyolysis-induced acute kidney injury, which may be related to its anti-inflammatory effect.
关键词
左卡尼汀 /
横纹肌溶解 /
急性肾损伤 /
免疫炎性反应
Key words
L-carnitine /
rhabdomyolysis /
acute kidney injury /
immune inflammation
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基金
重大灾害医学救援卫星综合应用服务示范项目,资助编号:发改办高技(2013)2140号
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