木犀草素对单侧输尿管梗阻模型大鼠肾脏的抗炎及抗纤维化作用

摘要

Objective To investigate whether luteolin ease anti-inflammatory and anti-fibrosis of unilateral ureter obstruction of kidney in rats and its therapeutic effect on obstructive nephropathy .Methods Thirty two SD rats were randomly assigned into four groups as follows :sham operation group(n= 8) ,model group(n= 8) ,dexamethasone group(n= 8) and luteolin group(n= 8) . The sham group were exposed to left ureter separation operation ,while the other three groups were treated with left ureter ligation operation .Then four groups received drug as the operation demanded .Rats were sacrificed at the 10th day after we had got the blood and collected obstructed lateral kidney .Then colorimetric determination was taken to test the changes of serum nitrogen and serum creatinine ,and the kidney tissue were stained with HE and Masson to assess histology pathological changes .We also assess the severity of renal interstitium by using the index of intestinal damage and fibrosis .Results Compared with sham group ,we could observe several changes in model group as follows :the obvious enlargement of the kidney ,cortex thinning ,the deformation of renal tubular ,and the evident inflammatory reaction ,as well as the significant increase of the index of intestinal damage and fibrosis inte-gral of renal interstitium increased(P< 0 .05) ,serum nitrogen and creatinine (P< 0 .05) .Similar to model group ,such changes were observed in the lueteolin group and dexamathasone group :rats′ kidney were enlarged ,inflammatory reaction ,the index of intestinal damage and fibrosis integral of renal interstitium decreased significantly(P< 0 .05) ,the luteolin group serum nitrogen and creatinine increased significantly (P< 0 .05) ,yet that in the dexametasone group was not significant ;contrasted with model group ,whereas , luteolin group and dexamethasone group kidneys′ ,volume diminished distinctly ,but much bigger than those in sham group ,cortex thinning was less obvious ,the inflammatory reaction weakened distinctly ,as well as the renal tubular decoration and the index of in-testinal damage .Fibrosis integral of renal interstitium decreased significantly ( P < 0 .05) ,the serum nitrogen and creatinine de-creased significantly (P < 0 .05) ,there was remarkable difference between the dexamethasone group and the luteolin group(P <0 .05) .Conclusion Luteolin can′t completely prevent or reverse unilateral ureter obstruction rat kidney tissue damaging and func-tional changing ,but it can ease the unilateral ureter obstruction rats inflammatory reaction ,kidney destruction as well as renal path-ological damaging .Its therapeutic effect is inferior than that of dexamethasone .%目的：观察木犀草素对单侧输尿管梗阻大鼠肾脏炎性反应和纤维化的影响及对梗阻性肾病的治疗作用。方法将雄性 SD 大鼠32只按照随机数字表分组方法分为假手术组（Sham 组，n＝8）、模型组（模型组，n＝8）、地塞米松组（n＝8）和木犀草素组（n＝8）。 Sham 组行左侧输尿管分离术，后3组行左侧输尿管结扎术。术后第1天按照要求开始给药，各组大鼠于手术后10 d 眶静脉取血并留取梗阻侧肾组织后处死，比色法检测血清尿素氮、肌酐的变化，HE 和 Masson 染色观察肾组织病理变化，并用间质损伤指数和肾小管间质纤维化积分定量观察肾组织损伤情况。结果与 Sham 组对比，模型组大鼠肾脏明显肿大、皮质明显变薄、肾小管变形明显、炎性反应明显，间质损伤指数、纤维化积分明显增加（P＜0．05），血尿素氮、血肌酐明显增加（P＜0．05）；木犀草素组和地塞米松组大鼠肾脏肿大、皮质变薄、肾小管变形、轻度炎性反应，两组间质损伤指数、纤维化积分明显增加（P ＜0．05），木犀草素组血尿素氮、血肌酐明显增加（P＜0．05），地塞米松组血尿素氮、血肌酐变化不明显。与模型组对比，木犀草素组和地塞米松组肾脏体积明显变小、皮质变薄程度较小、肾小管变形减轻、炎性反应明显减弱，间质损伤指数、纤维化积分明显降低（P＜0．05），血尿素氮、血肌酐明显降低（P＜0．05），木犀草素组和地塞米松素组两组差异有统计学意义（P ＜0．05）。结论木犀草素不能完全阻止或逆转单侧输尿管梗阻大鼠肾脏的组织结构损伤和功能改变，但是其能够减轻单侧输尿管梗阻大鼠肾脏的炎性反应、肾功能损害及病理损害，效果较地塞米松有一定的差异。