CAJ | 학술논문

目的：探讨维生素D对糖尿病肾病大鼠转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)和重组人胶原蛋白-1(collagen-1)表达的影响，进一步探讨以上3个基因在糖尿病肾病中相互作用以及维生素D对糖尿病肾病大鼠肾脏的保护作用。方法将54只雄性SD大鼠按随机数字表法分为正常对照组(18只)、模型组(18只)、治疗组(18只)。其中，模型组及治疗组大鼠均行糖尿病肾病造模，饲以高脂高糖饲料6周，空腹12 h后给予小剂量链腺佐菌素腹腔注射。注射1周后，不同日期测随机血糖(GLU)3次，若3次GLU均≥16.7 mmol/L为2型糖尿病大鼠。2型糖尿病成模后的大鼠在6周和7周时用尿微量蛋白试纸连续测大鼠晨尿3次以上，若为阳性，则为2型糖尿病肾病的大鼠。治疗组给予骨化三醇溶于0.05 mL花生油以0.03μg/(kg·d)灌胃37 d，模型组给予花生油灌胃37 d。处死大鼠，取肾脏，采用HE、电镜技术观测肾脏组织的形态学变化，采用实时荧光定量PCR技术(RT-PCR)评价肾脏TGF-β1、collagen-1及CTGF基因表达的变化。结果①模型组TGF-β1、collagen-1及CTGF基因表达高于正常对照组(P<0.05)，治疗组TGF-β1、collagen-1及CTGF基因表达明显低于模型组(P<0.05)。②采用HE、电镜技术可以看出治疗组病理组织形态学，尤其是组织结构完整性明显优于模型组。结论糖尿病肾病大鼠中，维生素D可以通过下调TGF-β1、collagen-1及CTGF基因的表达，对糖尿病肾病起保护作用。
목적：탐토유생소D대당뇨병신병대서전화생장인자-β1(TGF-β1)、결체조직생장인자(CTGF)화중조인효원단백-1(collagen-1)표체적영향，진일보탐토이상3개기인재당뇨병신병중상호작용이급유생소D대당뇨병신병대서신장적보호작용。방법장54지웅성SD대서안수궤수자표법분위정상대조조(18지)、모형조(18지)、치료조(18지)。기중，모형조급치료조대서균행당뇨병신병조모，사이고지고당사료6주，공복12 h후급여소제량련선좌균소복강주사。주사1주후，불동일기측수궤혈당(GLU)3차，약3차GLU균≥16.7 mmol/L위2형당뇨병대서。2형당뇨병성모후적대서재6주화7주시용뇨미량단백시지련속측대서신뇨3차이상，약위양성，칙위2형당뇨병신병적대서。치료조급여골화삼순용우0.05 mL화생유이0.03μg/(kg·d)관위37 d，모형조급여화생유관위37 d。처사대서，취신장，채용HE、전경기술관측신장조직적형태학변화，채용실시형광정량PCR기술(RT-PCR)평개신장TGF-β1、collagen-1급CTGF기인표체적변화。결과①모형조TGF-β1、collagen-1급CTGF기인표체고우정상대조조(P<0.05)，치료조TGF-β1、collagen-1급CTGF기인표체명현저우모형조(P<0.05)。②채용HE、전경기술가이간출치료조병리조직형태학，우기시조직결구완정성명현우우모형조。결론당뇨병신병대서중，유생소D가이통과하조TGF-β1、collagen-1급CTGF기인적표체，대당뇨병신병기보호작용。
Objective To explore the effect of vitamin D on the expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and restructuring of collagen-1 (collagen-1) in diabetic nephropathy rat, discuss their interaction in diabetic nephropathy, and the protective effect of vitamin D for the kidney of diabetic nephropathy rat. Methods 54 male SD rats were randomly divided into three groups: normal control group (n=18), model group (n=18), treatment group (n=18). The model group and treatment group rats were established diabetic nephropathy model, and fed with high fat diet for 6 weeks, then intraperitoneal injection of small dose streptozotocin after fasting for 12 hours. 1 week after injection, 3 times of blood glucose (GLU) on a different date were measured, if 3 times of GLU all≥16.7 mmol/L indicated that rats had type 2 diabetes mellitus. 6 and 7 weeks after type 2 diabetes mellitus model es-tablishment, trace protein urine dipstick was used for detection of the morning urine of rats for at least 3 times, if the results were positive, indicated that rats had type 2 dia-betic nephropathy. The treatment group was given 0.03μg/(kg·d) calcitriol dissolved in 0.05 mL peanut oil by intragastric administration for 37 d. The model group was given peanut oil by intragastric administration for 37 d. After treatment all rats were killed, and the kidneys were removed. HE, electron microscopy were used for morphological changes observation of renal tissue, real-time fluorescence quantitative PCR (RT-PCR) was used for e-valuation of expression changes of renal TGF-β1, collagen-1 and CTGF genes. Results ①The expression of TGF-β1, collagen-1 and CTGF genes in the model group were significantly higher than those in the normal control group (P<0.05), which in the treatment group were significantly lower than those in the model group (P<0.05).②The results of HE, electron microscopy showed that in the treatment group the pathological tissue morphology, especially organization-al structure integrity was better than that of model group significantly. Conclusion Vitamin D can down regulate the expression of TGF- β1, collagen-1 and CTGF genes, has protective effect on diabetic nephropathy for the diabetic nephropathy rats.