论文部分内容阅读
目的探讨蛋白激酶 C(PKC)-βⅠ,βⅡ在糖尿病肾病(DN)小鼠肾脏中各部位的分布、表达以及血管紧张素受体拮抗剂替米沙坦对其影响。方法 18只小鼠随机分为正常组、DN 组和治疗组(TG 组)。采用半定量免疫荧光技术检测肾小球内 PKC-βⅠ、βⅡ,转化生长因子(TGF-β1)和血管内皮细胞生长因子(VEGF)的表达情况,激光共聚焦及免疫印迹技术检测 PKC-βⅠ,βⅡ在肾组织中的分布与表达。结果与正常组相比,DN 小鼠近曲小管上皮细胞腔膜侧 PKC-βⅠ,-βⅡ的表达较强,而皮质和内髓集合管上皮细胞 PKC-βⅡ的表达消失;DN 小鼠肾皮质和外髓 PKC-β1的表达量较多(P<0.01),而肾皮质内 PKC-βⅡ的表达则明显较低(P<0.01)。半定量免疫荧光进一步表明,PKC-βⅠ、TGF-β1和 VEGF 在 DN 小鼠肾小球内的表达量明显高于正常组(分别上调0.48、0.20和0.24倍,均 P<0.01),而 PKC-βⅡ的表达则下调0.27倍(P<0.05),其中 PKC-β1的表达与 TGF-β1呈正相关(r=0.649,P=0.030)而与 VEGF 无关(r=0.387,P=0.079),PKC-βⅡ的表达与 TGF-β1、VEGF 均无关。替米沙坦能部分纠正上述变化。结论 (1)DN 小鼠肾组织中 PKC-βⅠ、βⅡ的表达和分布发生变化,提示它们参与 DN 近曲小管功能改变,其中 PKC-β1可能通过影响肾小球 TGF-β1的表达参与 DN 肾小球的肥大。(2)DN 时肾素血管紧张素系统的活性增加可能是 PKC-βⅠ,βⅡ异常激活的重要原因,替米沙坦可能通过部分改善 PKC-βⅠ,βⅡ的表达来实现其肾脏保护作用。
Objective To investigate the distribution and expression of protein kinase C (PKC) -βⅠ and βⅡ in various parts of the kidney of diabetic nephropathy (DN) mice and the effect of angiotensin receptor antagonist telmisartan on it. Methods Eighteen mice were randomly divided into normal group, DN group and treatment group (TG group). The expression of PKC-βⅠ, βⅡ, TGF-β1 and VEGF were detected by semi-quantitative immunofluorescence. The expressions of PKC-βⅠ, Distribution and Expression of β Ⅱ in Renal Tissue. Results Compared with the normal group, the expressions of PKC-βⅠ and -βⅡ in the proximal tubule epithelial cells of DN mice were stronger than that of the normal group, while the expressions of PKC-βⅡ in the cortical and medullary collecting duct epithelial cells disappeared. (P <0.01), while the expression of PKC-βⅡ in renal cortex was significantly lower (P <0.01). Semi-quantitative immunofluorescence further showed that the expression of PKC-βⅠ, TGF-β1 and VEGF in glomeruli of DN mice were significantly higher than those in normal mice (0.48,0.20 and 0.24 times, all P <0.01), while PKC The expression of PKC-β1 was positively correlated with TGF-β1 (r = 0.649, P = 0.030), but not with VEGF (r = 0.387, P = 0.079) The expression of -βⅡwas not related to TGF-β1 and VEGF. Telmisartan can partially correct the above changes. CONCLUSIONS: (1) The expression of PKC-βⅠ and βⅡ in DN mice changes, suggesting that they are involved in the function of DN proximal tubule. PKC-β1 may participate in DN kidney by affecting the expression of TGF-β1 in glomeruli Small ball of hypertrophy. (2) The increased activity of renin angiotensin system in DN may be an important reason for the abnormal activation of PKC-βⅠ and βⅡ. Telmisartan may achieve its renal protective effect by partially improving the expression of PKC-βⅠ and βⅡ.