锌制剂对糖尿病大鼠肾脏和肾脏组织中VEGF、MT及MMP-9表达的影响

目的：通过观察正常及糖尿病大鼠肾脏组织中血管内皮生长因子（VEGF）、金属硫蛋白（MT）及基质金属蛋白酶9（MMP-9）的表达，阐明补充外源性锌(Zn)制剂对糖尿病大鼠肾脏和肾脏组织中VEGF、MT及MMP-9表达的影响。方法： 将48只Wistar大鼠随机分为正常对照组（NC组）、阴性对照组（STZ组）、外源性锌干预糖尿病组（STZ+Zn组）及外源性锌干预正常组（Zn组），每组12只。其中STZ组及STZ+Zn组腹腔注射链脲菌素(STZ)制成糖尿病模型， STZ+Zn组、Zn组每周2次经口灌胃5 mg?kg-1的锌制剂，共16周。取双肾，计算肾指数；HE染色及免疫组织化学染色观察大鼠肾脏病理学改变及MMP-9、VEGF和MT在肾脏组织中的表达。结果：与NC组比较，STZ组和STZ+Zn组大鼠肾指数升高（P<0.05）；与STZ组比较，STZ+Zn组大鼠肾指数升高（P<0.05）；Zn组肾指数与NC组比较差异无显著性(P>0.05)。大鼠肾脏组织中存在VEGF、 MT 及MMP-9的表达，其中MMP-9和VEGF主要表达在远端肾小管，MT主要表达在近端肾小管；NC组、STZ组、STZ+Zn组及Zn组之间比较肾脏组织中VEGF、MT和MMP-9表达差异无显著性(P＞0.05)。结论：锌制剂可以导致糖尿病大鼠肾指数增大，但不影响健康小鼠的肾指数；肾脏组织中存在VEGF、MT及MMP-9的表达；外源性锌制剂干预后VEGF、MT及MMP-9在糖尿病模型中的表达无明显变化。

Effects of Zn on kidney of dibetic rats and expessions of VEGF,MT and MMP-9 in kidney tissues

Objective By observing the expressions of vascular endothelial growth factor(VEGF),metallothionein(MT),and matrix metalloprteinase-9(MMP-9)in the kidneys of normal and diabetic rats,the influences of exogenous Zn in kindey and the expessions of VEGF,MT and MMP-9 in kidney tissues of diabetic rats were explored.Methods Forty-eight Wistar rats were randomly divided into four groups(n=12):normal control(NC)group,negative control(STZ)group,external Zn intervention diabetic(STZ+Zn)group and external Zn intervention normal(Zn)group.The rat diabetic models were made through intraperitoneal injection of streptozotocin(STZ)in STZ and STZ+Zn groups.The rats in STZ+Zn and Zn groups were orally injected with 5 mg·kg-1of Zn sulphate twice a week.After fed for 16 weeks,the kidneys of rats were obtained and organ coefficient of kidney was calculated.The histopathological changes of kindeys and the expressions of MMP-9,VEGF and MT in kidney tissues were detected with immunohistochemistry method.Results Compared with NC group,the organ coefficients in STZ group and STZ+Zn group were increased(P< 0.05).Compared with STZ group,the organ coefficient in STZ+Zn group was increased(P<0.05).There was no difference of organ coefficient between STZ group and Zn group(P>0.05).The MMP-9,VEGF,and MT expressed in kidneys of rats.MMP-9 and VEGF mainly expressed in the distal renal tubule;and MT mainly expressed in the proximal renal tubulei.there was no difference of the expressions of MMP-9,VEGF,and MT in kidney tissues between various groups(P>0.05).Conclusion External Zn intervention can increase the organ cofficient of kidney in diabetic rats,but dosen't affect the organ coefficient of kindey in normal rats.The expressions of MMP-9,VEGF,and MT in kidney tissues of rats have no changes after external Zn intervention.