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目的:研究慢性肾衰时,大鼠血管平滑肌上钙激活钾(KCa)通道功能的变化。方法:将40只SD大鼠随机分为假手术组、病理6周组、病理10周组和病理14周组。对各病理组大鼠进行5/6肾切除致慢性肾衰,分别测定各组大鼠血清生化指标和尿蛋白水平,对其胸主动脉环进行血管张力反应性测定,并对胸主动脉KCa通道mRNA进行实时荧光定量PCR检测。结果:血生化和尿蛋白指标显示慢性肾衰造模成功。血管张力反应性测定中,各病理组在无药物干预条件下,由乙酰胆碱引起的舒张功能均较假手术组明显减弱(P<0.01);通过L-硝基-精氨酸甲酯(L-NAME)、吲哚美辛和KCa通道阻滞剂进行不同干预后发现,各病理组KCa通道功能均有所下降,导致血管舒张功能紊乱。病理组间比较显示,在L-NAME单独干预及L-NAME与吲哚美辛共同干预两种条件下,病理10周组血管最大舒张程度均明显低于病理6周组(P<0.05),而病理10周组与病理14周组间差异不大。PCR反应显示,与假手术组相比,各病理组KCa通道代表基因KCNMA1和KCNN2表达量均下降,但仅后者有极显著性差异(P<0.01)。各病理组间KCNMA1和KCNN2表达量均无显著性差异。结论:慢性肾衰会造成大鼠血管平滑肌KCa通道正常功能的改变,从而导致血管舒张功能受到损伤,损伤作用加重至10周时趋于稳定;慢性肾衰时血管平滑肌KCa通道mRNA表达的抑制作用未表现出有增龄变化。
Objective: To study the changes of calcium-activated potassium (KCa) channel function in rat vascular smooth muscle cells during chronic renal failure. Methods: Forty SD rats were randomly divided into sham operation group, pathological 6 weeks group, pathological 10 weeks group and pathological 14 weeks group. Rats in each pathological group were subjected to 5/6 nephrectomy for chronic renal failure. Serum biochemical indexes and urinary protein levels were determined in each group. Vascular tension reactivity was measured in the thoracic aorta rings, Channels mRNA for real-time fluorescence quantitative PCR detection. Results: Blood biochemistry and urinary protein index showed successful model of chronic renal failure. In the measurement of vascular tone reactivity, the diastolic function induced by acetylcholine in all pathological groups was significantly weaker than that in sham-operated group (P <0.01) in the absence of drug intervention. By the method of L-nitro-arginine methyl ester NAME), indomethacin and KCa channel blockers. The results showed that the function of KCa channel in each pathological group decreased, leading to the disorder of vasodilatation. Pathological comparison showed that under the condition of L-NAME intervention alone and L-NAME combined with indomethacin, the maximal vasorelaxation of the 10-week pathological group was significantly lower than that of the 6-week pathological group (P <0.05) There was no significant difference between the 10-week pathology and the 14-week pathology. PCR reaction showed that compared with the sham operation group, the expressions of KCN channel KCAMA1 and KCNN2 genes decreased in all pathological groups, but the latter ones had extremely significant difference (P <0.01). There was no significant difference in the expression of KCNMA1 and KCNN2 among the pathological groups. CONCLUSION: Chronic renal failure can cause the normal function of KCa channel in rat vascular smooth muscle, resulting in the vasodilation being damaged and the injury aggravating ten weeks to stabilize. The inhibition of KCa channel mRNA expression in chronic renal failure Did not show changes in aging.