青蒿素对实验性糖尿病大鼠肾脏PDGF-B表达上调的影响

Effect of Artemisinin on the upregulation of PDGF-B protein expression in the kidney of experimental diabetic rats

目的探讨青蒿素对实验性糖尿病大鼠肾脏血小板衍化生长因子-B(PDGF-B)表达上调的抑制作用。方法将36只雄性SD大鼠随机分为正常对照组(A组)、糖尿病非治疗组(B组)及糖尿病青蒿素治疗组(C组),B、C组采用腹腔单剂量注射链脲佐菌素(STZ)65 mg/kg建立糖尿病大鼠模型。C组给予青蒿素300 g/(kg·d)腹腔注射。于实验第3周、第6周各组分别宰杀6只大鼠,采用免疫组织化学染色法检测肾皮质PDGF-B的蛋白表达。并检测肌酐清除率(Ccr)、24 h尿白蛋白排泄率(UAER)及肾质量/体质量。肾组织制备电子显微镜切片以观察肾组织超微结构改变。结果 C组大鼠肾质量/体质量、Ccr、UAER均显著低于B组(P<0.05或0.01)。免疫组化染色发现B组大鼠肾组织PDGF-B表达显著上调(P<0.01),C组表达明显下调(P<0.01)。电镜示B组大鼠肾脏病变广泛,肾小球系膜细胞增生,系膜区增宽,基底膜增厚,脏层细胞肥大。C组大鼠肾脏超微结构异常显著减轻。结论青蒿素能减轻糖尿病大鼠肾脏病变,主要通过下调糖尿病大鼠肾组织PDGF-B表达来实现。

Objective It is to investigate the inhibitory effect of artemisinin on the upregulation of PDGF - B protein ex- pression in the kidney of experimental diabetic rats. Methods 36 male SD rats were randomly divided into normal control group （A group）, non-treatment diabetic group （B group）, and diabetic treated with Artemisinin group （C group）. The diabetic models of rats were established by STZ 65 mg/kg by intraperitoneal injection in group B and group C. Group C was given Arte- misinin 300 g/（ kg ~ d） by intraperitoneal injection. UAER, Ccr as well as the profile of kidney hypertrophy were observed af- ter 3, 6 weeks of treatment, while PDGF -B protein expression was measured by immunohistological staining. In addition, re- nal tissues were observed by transmission electron microscopy. Results Kidney/body weight ratio, Ccr, and UAER of the rats in group C were significantly lower than those in group B （P 〈 0.05 or 0.01 ）. Immumohistochemical staining results showed that the protein expression of PDGF - B （P 〈 0. O1 ） significantly increased in renal tissue in group B （ P 〈 0.01 ） , while de- creased in group C（ P 〈 O. 01 ）. Electron microscopy results showed that in the rats of group B, extensive kidney lesion, glo- merular mesangial cell proliferation and mesangial area broadening, thickening of basement membrane, dirty layer cell hyper- trophy were found, while in groupC, abnormal uhrastructure was significantly relieved. Conclusion Atemisinin can relieve re- nal lesions in experimental diabetic rats, which was partly through inhibiting PDGF- B expression in renal cortices.