PKCβ抑制劑通過影響巨噬細(xì)胞亞型的改變對腎缺血再灌注損傷起保護(hù)作用
發(fā)布時間：2018-08-29 18:56
【摘要】：目的:采用腎缺血再灌注損傷為模型,經(jīng)口給予蛋白激酶Cβ(PKCβ)抑制劑干預(yù),觀察PKCβ抑制劑對腎缺血再灌注損傷中炎性介質(zhì)及巨噬細(xì)胞等的影響,探討其對腎IRI的保護(hù)機(jī)制。方法:將購買的大鼠隨機(jī)分為三組,分別為腎缺血再灌注損傷模型組(A組),PKCβ抑制劑干預(yù)組(B組)和假手術(shù)組(C組)。A組予去右腎,左腎按常規(guī)方式即腎蒂鉗夾缺血60分鐘后恢復(fù)灌注24小時;B組予術(shù)前經(jīng)口腔給藥PKCβ抑制劑干預(yù);C組僅行開腹、60分鐘后關(guān)腹手術(shù)。術(shù)后24小時取下腔靜脈血及腎臟標(biāo)本進(jìn)行實驗研究:1.全自動生化儀檢測各組血清肌酐值及尿素情況;2.PAS染色觀察病理組織損傷嚴(yán)重程度;3.免疫組織化學(xué)法檢測腎損傷分子-1、腎乳頭狀抗原-1及誘生型一氧化氮合酶-1、精氨酸酶-1的表達(dá);結(jié)果:1.全自動生化儀檢測血清肌酐、尿素結(jié)果示:尿素值A(chǔ)、B組均較C組增高(P0.01),且A組水平高于B組(P0.01);同樣肌酐值A(chǔ)、B組也均高于C組(P0.01),但A組與B組比較無明顯差異(P0.05);2.腎組織PAS染色結(jié)果:A組腎間質(zhì)水腫、炎性細(xì)胞浸潤,腎小管嚴(yán)重破壞、結(jié)構(gòu)紊亂、管腔擴(kuò)張,可見小管刷狀緣丟失、管狀上皮細(xì)胞扁平、脫落,并有大量管型存在;B組:相較A組,小管結(jié)構(gòu)較清晰,腎間質(zhì)水腫及炎性細(xì)胞浸潤減輕,但仍可見部分小管結(jié)構(gòu)破壞,偶見管型;C組:小管結(jié)構(gòu)清晰、完整,未見管型及明顯間質(zhì)水腫,但組織間隙中可見少量炎性細(xì)胞浸潤。3.免疫組化檢測:KIM-1結(jié)果顯示在C組少量表達(dá),A組、B組表達(dá)均較C組明顯升高(P0.01),而A組又顯著強(qiáng)于B組(P0.01);RPA-1示A組在腎乳頭小管強(qiáng)陽性表達(dá),B組表達(dá)較A組明顯減輕(P0.01),C組微量或基本未見表達(dá)。同樣iNOS的表達(dá)也顯示A組明顯強(qiáng)于B、C組(P0.01),C組表達(dá)甚少,B組強(qiáng)于C組(P0.01);而在Arg-1的表達(dá)上B組較A、C組均強(qiáng)(P0.01),而A組又高于C組(P0.01)。結(jié)論:PKCβ抑制劑可以通過影響巨噬細(xì)胞亞型的變化而產(chǎn)生保護(hù)腎缺血再灌注損傷的作用。
[Abstract]:Objective: to observe the effects of protein kinase C 尾 (PKC 尾) inhibitor on inflammatory mediators and macrophages in renal ischemia-reperfusion injury and explore the protective mechanism of PKC 尾 on renal IRI. Methods: the rats were randomly divided into three groups: model group (group A), PKC 尾 inhibitor intervention group (group B) and sham operation group (group C). The left kidney was treated with oral administration of PKC 尾 inhibitor for 60 minutes after ischemia for 60 minutes and then restored to perfusion for 24 hours. Group C was treated with open abdominal surgery for 60 minutes and closed abdominal operation after 60 minutes. Blood samples of inferior vena cava and kidney were collected 24 hours after operation. The levels of serum creatinine and urea were detected by automatic biochemical instrument. 2. The severity of pathological tissue injury was observed by pas staining. The expression of renal injury molecule -1, papillary antigen 1 and inducible nitric oxide synthase 1 and arginase 1 were detected by immunohistochemistry. Serum creatinine was detected by automatic biochemical instrument. Urea value in group A was higher than that in group C (P0.01), and the level of creatinine in group A was higher than that in group B (P0.01). Similarly, creatinine level in group A was higher than that in group C (P0.01), but there was no significant difference between group A and group B (P0.05). Renal tissue PAS staining showed interstitial edema, inflammatory cell infiltration, serious destruction of renal tubules, structural disorder, dilatation of lumen, loss of brush edge of tubules, flattening and shedding of tubular epithelial cells in group A. There were a large number of tubules in group B: compared with group A, the tubule structure was clearer, renal interstitial edema and inflammatory cell infiltration were alleviated, but some tubules were still damaged. Occasionally, tubule structure was clear and complete in group C. No tubular and interstitial edema was found, but a small number of inflammatory cells infiltrated in the interstitial space. 3. Immunohistochemical analysis showed that the expression of KIM-1 in group A was significantly higher than that in group C (P0.01), while the expression of RPA-1 in group A was significantly stronger than that in group B (P0.01). The positive expression of KIM-1 in group A was significantly lower than that in group A (P0.01). Group A showed little or no expression. The expression of iNOS in group A was significantly higher than that in group C (P0.01), but the expression of Arg-1 in group B was stronger than that in group C (P0.01), and the expression of Arg-1 in group A was higher than that in group C (P0.01). Conclusion the effect of PKC 尾 inhibitor on renal ischemia-reperfusion injury may be induced by affecting the changes of macrophage subtypes.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R692
本文編號：2212103
[Abstract]:Objective: to observe the effects of protein kinase C 尾 (PKC 尾) inhibitor on inflammatory mediators and macrophages in renal ischemia-reperfusion injury and explore the protective mechanism of PKC 尾 on renal IRI. Methods: the rats were randomly divided into three groups: model group (group A), PKC 尾 inhibitor intervention group (group B) and sham operation group (group C). The left kidney was treated with oral administration of PKC 尾 inhibitor for 60 minutes after ischemia for 60 minutes and then restored to perfusion for 24 hours. Group C was treated with open abdominal surgery for 60 minutes and closed abdominal operation after 60 minutes. Blood samples of inferior vena cava and kidney were collected 24 hours after operation. The levels of serum creatinine and urea were detected by automatic biochemical instrument. 2. The severity of pathological tissue injury was observed by pas staining. The expression of renal injury molecule -1, papillary antigen 1 and inducible nitric oxide synthase 1 and arginase 1 were detected by immunohistochemistry. Serum creatinine was detected by automatic biochemical instrument. Urea value in group A was higher than that in group C (P0.01), and the level of creatinine in group A was higher than that in group B (P0.01). Similarly, creatinine level in group A was higher than that in group C (P0.01), but there was no significant difference between group A and group B (P0.05). Renal tissue PAS staining showed interstitial edema, inflammatory cell infiltration, serious destruction of renal tubules, structural disorder, dilatation of lumen, loss of brush edge of tubules, flattening and shedding of tubular epithelial cells in group A. There were a large number of tubules in group B: compared with group A, the tubule structure was clearer, renal interstitial edema and inflammatory cell infiltration were alleviated, but some tubules were still damaged. Occasionally, tubule structure was clear and complete in group C. No tubular and interstitial edema was found, but a small number of inflammatory cells infiltrated in the interstitial space. 3. Immunohistochemical analysis showed that the expression of KIM-1 in group A was significantly higher than that in group C (P0.01), while the expression of RPA-1 in group A was significantly stronger than that in group B (P0.01). The positive expression of KIM-1 in group A was significantly lower than that in group A (P0.01). Group A showed little or no expression. The expression of iNOS in group A was significantly higher than that in group C (P0.01), but the expression of Arg-1 in group B was stronger than that in group C (P0.01), and the expression of Arg-1 in group A was higher than that in group C (P0.01). Conclusion the effect of PKC 尾 inhibitor on renal ischemia-reperfusion injury may be induced by affecting the changes of macrophage subtypes.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R692
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