摘要
目的:观察柿叶黄酮对大鼠糖尿病肾组织中转化生长因子-β_1(TGF-β_1)和基质金属蛋白酶-9(MMP-9)的影响,并探讨其作用机制。方法:50只SD大鼠ip链脲佐菌素(STZ)溶液120 mg·kg^(-1),对大鼠进行糖尿病大鼠模型造模。随机将造模成功大鼠分为模型组,氨基胍组(0.1 g·kg^(-1)·d^(-1)),柿叶黄酮高、中、低剂量组(400,200,100 mg·kg^(-1)),每组10只大鼠,另设正常组大鼠10只。氨基胍组、柿叶黄酮组ig给药(1次/天),连续给药12周,期间给予模型组和正常组等体积生理盐水。给药前及给药期间每隔3周测大鼠24 h尿蛋白含量及空腹血糖(FBG),末次给药2 h后处死大鼠,苏木素-伊红(HE)染色观察肾脏病理学变化,采用生化仪测定肾组织匀浆中丙二醛(MDA),超氧化物歧化酶(SOD),糖基化终产物(AGEs)及果糖胺(FTS)水平,蛋白质免疫印迹(Western blot)法检测肾脏组织中TGF-β_1和MMP-9的蛋白表达。结果:与正常组比较,模型组中大鼠24 h尿蛋白含量及FBG含量持续增高,肾组织中MDA,AGEs,FTS含量升高明显,SOD水平明显下降(P<0.05,P<0.01);与模型组比较,柿叶黄酮各剂量组明显降低24 h尿蛋白含量及FBG含量及肾组织中MDA,AGEs,FTS含量,明显升高SOD水平(P<0.05,P<0.01),明显下调肾脏组织中TGF-β_1和上调MMP-9的蛋白水平(P<0.05),其中柿叶黄酮高剂量组作用较为明显。结论:柿叶黄酮对糖尿病肾病大鼠有一定保护作用,其机制与柿叶黄酮的降糖、降脂、降低氧化应激水平及非酶糖基化的作用以及抑制TGF-β_1和MMP-9蛋白相关。
Objective： To investigate the protective mechanism of flavonoid from Diospyros kaki leaves （FDKL） on transforming growth factor-β1（TGF-β1） and matrix metalloproteinase-9（MMP-9） of diabetic nephropathy（DN） rats. Method： The 50 DN rats were intraperitoneally injected with streptozotocin（STZ） （120 mg·kg^-1） to establish the rat diabetic model. The blood glucose was measured before modeling, and the DN rats were randomly divided into model group, aminoguanidine group, FDKL low, medium and high-dose （100, 200, 400 mg·kg^-1） groups, with 10 rats in each group. Normal group was composed of 10 normal rats. The rats were administrated with the corresponding medicines for 12 weeks, and the rats of normal and model groups were given equal volume of normal saline. Before and during the administration, the 24 h urine protein and fasting blood glucose （FBG） were determined every 3 weeks. Two hours later after the last administration, the levels of methane dicarboxylic aldehyde （MDA）, superoxide dismutase （SOD）, advanced glycation end products （AGEs） and fructosamine （FTS） in kidney tissues were tested after the treatment. The changes of kidney morphology were tested through HE-staining. The expressions of TGF-β1 and MMP-9 in kidney tissues were detected using Western blot. Result： Compared with the normal group, the model group showed continuous increase in 24 h urine protein and FBG content, and the levels MDA, AGEs, FTS in kidney tissues, and significantly decrease in SOD （P〈0.05, P〈0.01）.Compared with the model group, all of FDKL groups showed significant reduction in 24 h urine protein and the levels MDA, AGEs, FTS in kidney tissues, and significant increase in SOD （P〈0.05, P〈0.01）, notable decrease in TGF-β1 in kidney tissues, and up-regulation in MMP-9 （P〈0.05）, particularly FDKL high-dose group. Conclusion： FDKL has a protective effect on diabetic nephropathy rats, and its mechanisms are associated with the decrease in blood glucose, lip
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2016年第16期139-143,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
广西自然科学基金青年项目(2013JJBA40062)
关键词
柿叶黄酮
糖尿病肾病
转化生长因子-Β1
基质金属蛋白酶-9
flavonoid from Diospyros kaki leaves
diabetic nephropath
transforming growth factor-β1
matrix metalloproteinase-9
