麻醉和手术对老年大鼠脑内淀粉样β蛋白转运相关受体及降解酶表达的影响

Influence of anesthesia and surgery on the expression of transport receptors and catabolic enzymes of amyloid β-protein in aged rats

目的探讨老年大鼠术后脑内淀粉样β蛋白(Aβ)转运相关受体及降解酶表达的变化。方法健康SD大鼠100只,按鼠龄随机分为老年对照组(n=10)、老年手术组(n=40)、青年对照组(n=10)和青年手术组(n=40)。对照组不接受麻醉和手术。手术组在2%七氟醚麻醉下接受肝叶切除术后继续麻醉2h,分别于术后1、3、7、15d处死大鼠取材,应用免疫组化技术分析海马内低密度脂蛋白受体相关蛋白1(LRP-1)、高级糖基化终产物受体(RAGE)和大脑皮质内胰岛素降解酶(IDE)、中性内肽酶(NEP)的表达水平,应用定量RT-PCR技术测定海马内IDE mRNA和NEP mRNA的表达水平。结果与老年对照组比较,老年手术组大鼠术后各时点LRP-1、NEP和NEP mRNA表达均明显降低,RAGE表达明显升高,术后1d和15d时IDE表达明显降低,3d和7d时IDE mRNA表达明显降低,15d时IDE mRNA表达明显升高。与青年对照组比较,青年手术组大鼠术后各时点IDE mRNA表达明显降低,RAGE和NEP mRNA表达明显升高,术后3d、7d和15d时LRP-1表达明显降低,术后1d、3d时IDE表达明显降低,15d时IDE表达明显升高,术后1d时NEP表达明显升高,3d、7d和15d时NEP表达明显降低。结论麻醉和手术对老年大鼠脑内Aβ的向外转运能力和酶降解能力均有明显抑制作用,而对青年大鼠的影响相对较轻。

Objective To investigate the expression changes in transport receptor and catabolic enzymes of amyloid β-protein （Aβ） in the brain of aged rats after surgery. Methods One hundred healthy SD rats were randomly divided into 4 groups according to their ages： aged control group （n=10）, aged surgery group （n=40）, young control group （n=10）, and young surgery group （n=40）. Rats in surgery group underwent hepatic lobectomy under anesthesia with 2% sevoflurane, followed by a 2-hour continuous anesthesia after the surgery, and then sacrificed on the 1st, 3rd, 7th and 15th day after surgery to obtain specimens. The expression of low-density lipoprotein receptor-related protein 1 （LRP-1） and receptor for advanced glycation end products （RAGE） in the hippocampus, and the expression of insulin-degrading enzyme （IDE） and neprilysin （NEP） in the cerebral cortex were determined by immunohistochemistry. The mRNA expression of IDE and NEP in the hippocampus was determined with RT-PCR. Results Compared with aged control group, the expression ofLRP-1, NEP and NEP mRNA decreased and the expression of RAGE increased at each time point, the expression oflDE decreased at 1st and 15th day after surger）5 and the expression oflDE mRNA decreased at 3rd and 7th day and increased at 15th day after surgery in aged surgery group （P〈0.05, P〈 0.01）. Compared with young control group, the expression of IDE mRNA decreased and expressions of RAGE and NEP mRNA increased at each time point, the expression of LRP-1 decreased at 3rd, 7th and 15th day, the expression oflDE decreased at 1st, 3rd day and increased at 15th day, and the expression of NEP increased at 1st day and decreased at 3rd, 7th and 15th day after surgery in young surgery group （P〈0.05, P〈0.01）. Conclusion The procedure of anesthesia and surgery could significantly inhibit the outward transport and enzymatic degradation of Aβ in the brain of aged rats, and this effect is less evident in young rats.