核因子-κB与诱导型一氧化氮合酶在格列喹酮干预治疗糖尿病大鼠肾脏的表达

Expression of NF-κB and iNOS in the Kidney of Diabetic Rats Treated with Glurenorm

目的探讨糖尿病肾脏病变与格列喹酮干预治疗、核因子-κB(NF-κB)活化及诱导型一氧化氮合酶(iNOS)表达之间的关系。方法雄性SD大鼠40只随机分成对照组(A组)、糖尿病组(B组)、格列本脲干预组(C组)和格列喹酮干预组(D组)各10只。糖尿病模型按经典的60 mg.kg-1剂量一次性腹腔内注射链脲菌素制备,于12周末处死大鼠,留取肾脏标本,观测肾脏病理改变并用免疫组化法分析NF-κB及iNOS表达。结果肾脏病理结果显示,与对照组相比,其余3组均有不同程度肾脏病变,其中B组肾脏病理改变最明显,C组较明显,D组较轻;免疫组化分析结果显示NF-κB和iNOS表达在D组与B、C组差异有显著性(P<0.05)。结论NF-κB及iNOS伴随着肾脏病理学改变而持续活化,可能在糖尿病肾病发生中有重要作用,而格列喹酮可以通过抑制炎症因子的表达起到肾脏保护作用。

Objective To probe into the relationship between the activation of the transcription factor nuclear factorkappa B （NF-κB） and expression of inducible nitric oxide synthase （iNOS） and the treatment of diabetic nephropathy with glurenorm in rats. Methods Forty Sprague-Dawley rats were randomly divided into 4 equal groups： the control group （ group A） ,diabetes model group （group B）, glibenclamide treatment group （group C） and glurenorm treatment group （group D）. A model of diabetes was set up in each of the rats of groups B, C and D by a single intraperitoneal injection of 60mg·kg^-1 of streptozotocin（STZ）. Rats of group C and group D were then given each 1 mg·kg^-1 of glibenclamide and 10mg·kg^-1 of glurenorm, respectively, administered by gastrogavage b. i： d. , for 12 consecutive weeks. Rats of group A were given each an equivalent volume of 0. 1 mmol·L^-1 of citric acid buffer solution, administered by intra peritoneal injection, b. i. d. , for 12 consecutive weeks. The animals were sacrificed at the end of the 12th week and the kidneys were taken for histopathological examination and assay of the activity of NF-κB and expression of iNOS with immunohistochemical methods. Results Histopathologic changes in varying degrees were demonstrated in the kidneys from animals of group B, C and D as compared with those from rats of group A. These changes were most pronounced in the kidneys from rats of group B while those in kidneys from rats of group C and group D were more trifling. The results of immunohistochemical analysis revealed that, the expression of NF- κB in kidneys from rats of group D[ the percentage of positive cells was （ 19.58 ±4.94） % ] was lower than that in the kidneys from rats of group B[ （42.17 ± 8.52 ）% ] （P 〈 0.01 ）. The expression of iNOS in the kidneys from rats of group D [ the value of absorbance was（0. 167 3 ±0.012 2） ] was significantly lower than that in the kidneys from rats of group B[ （0.325 4 ±0.027 6） ] （ P 〈 0.05 ）. Conclusion The sustained activation of NF-κB and iNOS along with the progress of pathological changes in the diabetic kidney may play an important role in the development of diabetic nephropathy and glurenorm may exert protective effects on the kidney by inhibiting the expression of NF-κB and iNOS.