中药四毒清抑制LPS性肾脏损伤的机制研究

目的：研究中药复方四毒清防治内毒素性肾功能衰竭的作用机制。 方法： 将小鼠随机分成对照组、LPS组、四毒清防治组和四毒清组，用水（0.2 mL/10 g BW）或四毒清（1 000 g/L, 0.2 mL/10 g BW）灌胃3 d，每天2次, 第3 d灌胃后2 h，腹腔注射LPS(30 mg/kg，0.2 mL/10 g BW)或生理盐水（0.2 mL/10 g BW），腹腔注射后2 h，再用水或四毒清（0.2 mL/10 g）灌胃1次。测定各组小鼠血清肌酐（Cr）和尿素氮（BUN）的含量，观察肾脏超微结构，肾组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性的变化， 并用半定量RT-PCR方法测定肾组织细胞间黏附分子-1(ICAM-1) mRNA的表达。 结果： LPS引起小鼠血清Cr和BUN含量明显升高，肾脏近曲小管出现明显病理改变。四毒清有效降低LPS攻击小鼠血清Cr和BUN的含量，明显减轻近曲小管的损伤。LPS组小鼠肾组织MDA含量和ICAM-1 mRNA的表达显著高于对照组，而四毒清防治组肾组织MDA含量和ICAM-1 mRNA的表达明显低于LPS组，四毒清处理能显著升高肾组织SOD的活性。 结论： 中药四毒清防治内毒素性肾功能衰竭的作用机制与其升高肾组织SOD的活性、减轻肾组织氧化损伤并抑制肾脏ICAM-1 mRNA的表达有关。

Multiple mechanisms mediates the inhibitory effect of siduqing on lipopolysaccharide-induced acute renal injury in mice

AIM: To investigate the mechanisms by which siduqing, a Chinese medicine, protects against lipopolysaccharide (LPS)-induced acute renal dysfunction. METHODS: Mice were divided randomly into control, LPS, siduqing treatment and siduqing groups, and treated intragastrically with siduqing at a dose of (1 000) g/L (0.2 (mL/10 g) body weight) or distilled water (0.2 (mL/10) g body weight) twice a day for 3 days, LPS (30 mg/kg) or normal saline was injected intraperitoneally on day 3, followed by intragastrical administration with siduqing at a dose of (1 000) g/L (0.2 (mL/10 g) body weight) or distilled water (0.2 (mL/10 g) body weight). Blood was collected for determining urea nitrogen (BUN) and creatinine (Cr) contents, renal tissue for examining superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. In addition, electron microscopy was used to examine the ultrastructure changes in kidney, and RT-PCR was performed to detect renal intercellular adhesion molecule-1 (ICAM-1) mRNA expression. RESULTS: LPS significantly increased serum urea nitrogen (BUN) and creatinine (Cr) contents, and produced an obvious pathological change in renal ultrastructure, which were significantly attenuated by siduqing treatment. Moreover, siduqing treatment increased renal SOD activity, also markedly suppressed an increase in renal MDA production and ICAM-1 mRNA expression induced by LPS. CONCLUSION: These results suggest that siduqing protects against LPS-induced acute renal injury through inhibiting ICAM-1 mRNA expression, enhancing renal SOD activity and attenuating oxidant stress.