摘要
目的:观察富硒黄芪多糖对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠肾小管上皮细胞转分化的影响。方法:将50只STZ诱导的SPF级雄性糖尿病大鼠随机分为模型组、吡格列酮组和富硒黄芪多糖低、中、高剂量组,每组10只,正常组10只大鼠不进行造模。富硒黄芪多糖低、中、高剂量组按100、200、400 mg/kg灌胃,正常组及模型组灌胃等体积生理盐水,吡格列酮组按10 mg/kg灌胃吡格列酮。每天灌胃1次,连续干预4周。造模前及造模后第0、2、4周记录各组大鼠一般状况、检测尿微量白蛋白(urinary albumin,UAlb)和血糖。干预结束后,采用苏木精-伊红染色法(hematoxylin-eosin staining)观察各组大鼠肾脏组织形态学变化情况;测定各组大鼠血清肌酐(serum creatinine,SCr)、尿素氮(blood urea nitrogen,BUN)和血尿酸(uric acid,UA)表达水平;荧光定量PCR检测各组大鼠肾组织Ⅰ型胶原、Ⅲ型胶原、纤连蛋白(Fibronectin,FN)mRNA表达水平;免疫组化法(immunocytochemistry,IHC)检测各组大鼠肾组织α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、E-钙黏蛋白(E-cadherin)表达。结果:与模型组比较,富硒黄芪多糖中、高剂量组及吡格列酮组大鼠血糖、24 h UAlb于造模后第2周明显下降(P<0.05),血清SCr、BUN及UA表达降低(P<0.05),富硒黄芪多糖高剂量组及吡格列酮组大鼠肾组织中Ⅰ型胶原、Ⅲ型胶原、FN表达均降低(P<0.05),E-cadherin表达升高(P<0.05),富硒黄芪多糖低、中、高剂量组及吡格列酮组大鼠肾组织中α-SMA表达下降(P<0.01),肾小球数量增多,细胞外基质减少;与吡格列酮组比较,黄芪多糖高剂量组大鼠24 h Ualb、血清SCr、BUN、UA水平及Ⅰ型胶原、Ⅲ型胶原、FN表达水平、E-cadherin和α-SMA蛋白表达变化均不明显(P>0.05),肾小球数量减少,细胞外基质减少。结论:富硒黄芪多糖可降低STZ诱导的糖尿病大鼠血糖,具有抑制糖尿病大鼠肾小管上皮细胞转分化的作用。
Objective:To observe the effects of selenium-enriched astragalus polysaccharide on the transdifferentiation of renal tubular epithelial cells in diabetic rats induced by STZ.Methods:All 50 SPF grade male rat models with diabetes mellitus induced by STZ were randomized into the model group,pioglitazone group,low,medium and high doses groups of astragalus polysaccharide with ten rats in each group,ten rats in the normal group were unhandled.Low,medium and high doses groups of astragalus polysaccharide were drenched at 100,200 and 400mg/kg,the normal group and the model group accepted gastric gavage of equal volume of saline,and pioglitazone group was given pioglitazone by gavage at 10 mg/kg,they accepted gastric lavage once each day,and four weeks of intervention consecutively.To observe the general condition of the rats in different groups before modeling,at the zero,second and fourth weeks after modeling,to test UAlb and blood glucose.By the end of intervention,HE staining was applied to observe the histomorphological changes in the kidney in different groups;to measure the expressions of SCr,BUN and UA in the rats of different groups;fluorescence quantitative PCR was used to detect mRNA expressions of collagen type Ⅰ,collagen type Ⅲ and fibronectin(FN)in rat kidney tissues of various groups;IHC was adopted to measure the expressions ofα-SMA and E-cadherin in renal tissue of the rats in different groups.Results:Compared with the model group,the levels of blood glucose and 24h UAlb decreased obviously at the 2nd week after the modeling in medium and high doses groups of astragalus polysaccharide,and pioglitazone group(P<0.05),the expressions of SCr,BUN and UA reduced(P<0.05),the expressions of collagen type I,collagen type III and FN lowered in renal tissue of high dose group of astragalus polysaccharide and pioglitazone group(P<0.05),the expressions of E-cadherin increased(P<0.05),the expressions ofα-SMA reduced in low,medium and high doses groups of astragalus polysaccharide,and pioglitazone group(P<0.01),the number of glomeruli increased significantly,extracellular matrix reduced obviously;compared with pioglitazone group,the levels of 24 h UAlb,serum SCr,BUN and UA,the expressions of collagen type I,collagen typeⅢand FN,E-cadherin andαSMA changed insignificantly in high dose group of astragalus polysaccharide(P>0.05),the number of glomeruli decreased,and extracellular matrix reduced.Conclusion:Seleniumenriched astragalus polysaccharide could reduce the levels of blood glucose in STZ-induced DM rats,possessing the effects of inhibiting the transdifferentiation of renal tubular epithelial cells.
作者
王祖华
李钦
颜春鲁
刘轩
杨丽霞
李海东
WANG Zuhua;LI Qin;YAN Chunlu;LIU Xuan;YANG Lixia;LI Haidong(Gansu Province Health School,Lanzhou 730060,China;Gansu University of Chinese Medicine,Lanzhou 730000,China;Gansu Provincial Academy of Chinese Medicine,Lanzhou 730050,China;Weiyuan County Kangrong Chinese Medicine Technology Ltd.,Weiyuan 748200,China)
出处
《西部中医药》
2024年第9期7-11,共5页
Western Journal of Traditional Chinese Medicine
基金
甘肃省高等学校创新基金项目(2023A-298)
甘肃省中医药科研课题(GZKP-2022-41)。
关键词
糖尿病
肾小管上皮细胞转分化
富硒黄芪多糖
链脲佐菌素
大鼠
diabetes mellitus
transdifferentiation of renal tubular epithelial cells
selenium-enriched astragalus polysaccharide
STZ
rat
