PKCβ抑制剂对小鼠肾移植后肾组织炎症因子的影响

发布时间：2018-06-21 00:40

本文选题：蛋白激酶Cβ + 炎症趋化因子　；参考：《遵义医学院》2014年硕士论文

【摘要】：目的：通过建立小鼠肾移植模型，研究PKCβ受到抑制时移植肾内细胞间质趋化因子及外周血效应细胞相应指标变化，来探讨炎症反应可能的影响机制。方法：建立小鼠异质移植（allograft）和同质移植（isograft）的肾移植模型，将其分为异质移植对照组、异质移植PKCβ抑制剂治疗组和同质移植对照组。PKCβ抑制剂治疗组术前1天予PKCβ抑制剂灌胃，其余两组均予等量生理盐水灌胃，三组小鼠均于术后一天取移植肾后处死。用免疫组织化学法检测白细胞介素4（Interleukin4，IL-4）、白细胞介素8（Interleukin8，IL-8）、单核细胞趋化蛋白1（Monocyte chemotacticprotein-1， MCP-1）、巨噬细胞移动抑制因子（Macrophage migration inhibitoryfactor,MIF）、白细胞趋化因子（Leukocyte chemotactic factor，，LCF）、白细胞移动抑制因子（Leukocyte migration inhibitory factor，LIF）这些趋化因子的表达；用逆转录聚合酶链反应（RT－PCR）来检测LCF、低氧诱导因子1（Hypoxia inducible factor1，HIF-1）、MCP-1、IL-8、LIF、MIF、氧合血红蛋白1（Oxygenated hemoglobin1，HO-1）的表达情况。结果： 1.免疫组化提示：异质移植对照组IL-4、IL-8、MCP-1、MIF、LCF高表达，异质移植PKCβ抑制剂预治疗组和同质移植肾对照组表达明显减少；异质移植PKCβ抑制剂预治疗组表达较异质移植对照组明显降低（P0.01），异质移植对照组表达较同质移植组表达明显增高（P0.01）。异质移植PKCβ抑制剂预治疗组与同质对照组LIF高表达，异质移植对照组表达明显减少；异质移植PKCβ抑制剂预治疗组表达较异质移植对照组明显增高（P0.01），异质移植对照组表达较同质移植组表达明显降低（P0.01）。 2.RT－PCR结果提示：异质移植对照组IL-8、、MCP-1、LCF高表达，异质移植PKCβ抑制剂预治疗组和同质移植肾对照组表达明显减少；异质移植PKCβ抑制剂预治疗组表达较异质移植对照组明显降低（P0.05），异质移植对照组表达较同质移植组表达明显增高（P0.05）。异质移植PKCβ抑制剂预治疗组与同质对照组HIF、MIF、LIF高表达，异质移植对照组表达明显减少；异质移植PKCβ抑制剂预治疗组表达较异质移植对照组明显增高（P0.05），异质移植对照组表达较同质移植组表达明显降低（P0.05）。同质对照组HO-1高表达，异质移植PKCβ抑制剂预治疗组表达明显减少；异质移植PKCβ抑制剂预治疗组表达较异质移植对照组明显增高（P0.05），异质移植对照组表达较同质移植组表达明显降低（P0.05）。结论：PKCβ受到抑制时，炎症抑制因子表达升高，移植肾内肾间质炎症趋化因子的表达降低，PKC beta抑制剂对移植术后是通过减少炎症趋化因子的表达来抑制细胞浸润或增加炎症抑制因子的表达来减轻炎症反应，从而对移植肾起到保护与修复的作用。
[Abstract]:Aim: to study the changes of cytoplasmic chemokines and peripheral blood effector cells in renal allograft when PKC 尾 is inhibited, and to explore the possible mechanism of inflammatory response. Methods: the models of allograft and isograft in mice were established and divided into three groups: the control group, the PKC 尾 inhibitor treatment group and the homogenous transplantation control group. The PKC 尾 inhibitor was administered intragastric 1 day before the operation in the PKC 尾 inhibitor treatment group, and the PKC 尾 inhibitor therapy group was given intragastric administration one day before the operation. The other two groups were given the same amount of normal saline intragastric perfusion, and all the three groups were killed on the first day after operation. Immunohistochemical method was used to detect interleukin 4 (IL 4), interleukin 8 (IL 8), monocyte chemoattractant protein-1 (MCP 1), macrophage migration inhibitory factor (MIF), leukocyte chemoattractant factor (LCFF), leukocyte chemotactic factor (LCF), monocyte chemoattractant protein 1 (Monocyte chemoattractant protein-1), macrophage migration inhibitory factor (MIF), leukocyte chemoattractant factor (LCFF) and monocyte chemoattractant protein 1 (Monocyte chemoattractant protein-1). The expression of some chemokines; Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of LCFCs, hypoxia inducible factor-1 (HIF-1), MCP-1, IL-8, and oxygenated hemoglobulin 1 (HO-1). Results: 1. Immunohistochemistry showed that the expression of IL-4, IL-8, MCP-1, MIFF-LCF in the heterogeneous transplantation group was significantly lower than that in the PKC 尾 inhibitor pretreated group and the homogenous allograft control group. The expression of PKC 尾 inhibitor in the heterogeneous transplantation group was significantly lower than that in the heterogeneous transplantation group, and the expression of P0.01 in the heterogeneous transplantation group was significantly higher than that in the homogenous transplantation group. The expression of LIF in the PKC 尾 inhibitor pretreated group and the homogenous control group was higher than that in the heterogeneous transplantation control group. The expression of PKC 尾 inhibitor in heterogeneous transplantation group was significantly higher than that in heterogeneous transplantation control group, and the expression of P0.01in heterogeneous transplantation group was significantly lower than that in homogenous transplantation group. 2. RT-PCR results showed that IL-8 / MCP-1 / LCF expression was significantly higher in heterogeneous transplantation control group than that in heterogenous transplantation group. The expression of PKC 尾 inhibitor in heterogeneous transplantation group was significantly lower than that in heterogeneous transplantation group, and that in heterogeneous transplantation group was significantly higher than that in homogenous transplantation group. The high expression of HIF-MIFFIF was observed in the PKC 尾 inhibitor pretreated group and the homogenous control group, while the expression in the heterogeneous transplantation control group was significantly decreased. The expression of PKC 尾 inhibitor in heterogeneous transplantation group was significantly higher than that in heterogeneous transplantation group, and the expression of P0.05 in heterogeneous transplantation group was significantly lower than that in homogenous transplantation group. The high expression of HO-1 in the homogenous control group and the decrease in the expression of PKC 尾 inhibitor in the heterogeneous transplantation group; The expression of PKC 尾 inhibitor in heterogeneous transplantation group was significantly higher than that in heterogeneous transplantation group, and the expression of P0.05 in heterogeneous transplantation group was significantly lower than that in homogenous transplantation group. Conclusion the expression of inflammatory inhibitory factor increased when the PKC 尾 was inhibited. The expression of inflammatory chemokines in renal interstitial cells decreased after transplantation, the expression of inflammatory chemokines was reduced by reducing the expression of inflammatory chemokines or increasing the expression of inflammatory inhibitors. Thus, the graft plays a protective and repair role.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R699.2

【参考文献】