發(fā)布時間：2018-05-27 14:33

  本文選題：PTX3 + 足細(xì)胞��； 參考：《山東大學(xué)》2017年博士論文

【摘要】：研究背景及目的糖尿病是一種全球性疾病,國際糖尿病聯(lián)盟數(shù)據(jù)顯示,糖尿病的患病率在全世界范圍呈上升趨勢,目前患病率是8.8%,中國糖尿病患者人數(shù)為1.09億人,居全球首位,并且增長速度非�？�。大約有三分之一的病人發(fā)展成糖尿病腎病(diabetic nephropathy, DN ),DN屬于一種微血管病變,是造成患者死亡、殘疾的原因之一,也是終末期腎病的主要原因。因而進(jìn)一步研究糖尿病腎病的發(fā)生發(fā)展機制,尋求新的治療靶點和治療策略顯得尤為重要。DN的發(fā)病機制尚不明確,高血糖、高血脂、高血壓等多種因素參與糖尿病腎病的發(fā)生與發(fā)展,這些因素誘導(dǎo)多種炎性介質(zhì)分泌,促進(jìn)炎性細(xì)胞聚集導(dǎo)致DN出現(xiàn)免疫損傷,因此免疫系統(tǒng)激活和微炎癥狀態(tài)是目前較一致認(rèn)可的DN發(fā)病機制。正五聚蛋白3 (PTX3)是一種與C-反應(yīng)蛋白(CRP)和血清淀粉樣蛋白A(SAP)同屬于正五聚蛋白超家族的急性炎癥蛋白,由多種炎癥免疫細(xì)胞如中性粒細(xì)胞、巨噬細(xì)胞、樹突樣細(xì)胞和內(nèi)皮細(xì)胞等分泌或合成。CRP和SAP屬于短鏈正五聚蛋白,而PTX3屬于長鏈正五聚蛋白,在多種炎癥相關(guān)性疾病如微生物感染、自身免疫性疾病、動脈粥樣硬化等發(fā)揮著重要作用,它能夠通過模式識別、激活補體等機制發(fā)揮調(diào)理素和調(diào)節(jié)炎癥的功能。在急慢性感染性疾病中,PTX3和CRP可以作為標(biāo)志物在血液中很快升高,在一些無菌性炎癥中,它的水平可以更直接的反映血管炎癥狀態(tài)。最近,一些臨床研究表明,升高的血漿PTX3水平與心血管疾病和慢性腎臟病(CKD)有關(guān)。PTX3水平與體重指數(shù)(BMI)呈負(fù)相關(guān)表明PTX3可能在肥胖和代謝綜合征中起到一定作用。最近,AbuSemanN等研究表明,血漿PTX3水平的降低與2型糖尿病和糖尿病腎病有關(guān)。然而,目前的研究只集中在內(nèi)源性PTX-3水平表達(dá)的升高或是沉默與其他疾病的關(guān)系,對于PTX3治療作用的研究卻不多,只有零星的研究發(fā)現(xiàn),PTX3能有效預(yù)防巨細(xì)胞病毒感染,減少肺部曲霉菌感染,降低膿毒血癥小鼠模型的病死率等。在急性心肌梗動物模型中具有保護(hù)心臟的作用,可能與PTX3有抗動脈粥樣硬化有關(guān)。Lech M等研究發(fā)現(xiàn),內(nèi)源性或外源性PTX3能夠減輕小鼠缺血再灌注后的急慢性腎損傷�；谏鲜霰尘�,本研究第一部分探討PTX3是否具有減輕糖尿病腎病的腎損傷作用。材料與方法1.糖尿病腎病(DN)模型的建立24只8-12周齡雄性C57BL/6小鼠,6只正常飼養(yǎng)小鼠為正常對照組(NC組)。18只小鼠腹腔注射鏈脲佐菌素STZ (50mg/kg)連續(xù)5天,定期檢測血糖和尿蛋白。STZ注射4周后經(jīng)化驗證實DN小鼠模型建模成功,進(jìn)行干預(yù)分組,分為三組,PTX3組(n=6),DN小鼠建模成功后腹腔注射Recombinant PTX3 (0.5 mg/kg),每日一次,共注射4周;Anti-PTX3組(n=6),為中和內(nèi)源性PTX3,建模成功后腹腔注射抗鼠PTX3單克隆抗體(anti-mouse PTX3 mAb,0.2 mg/kg)每日一次,共注射4周;Control組(n=6)為糖尿病腎病小鼠對照組,腹腔注射同等劑量的緩沖液;干預(yù)4周(即STZ給藥8周)后處死所有小鼠,藥物干預(yù)前(STZ給藥4周)和干預(yù)后(STZ給藥8周)分別留取血樣檢測血肌酐和24小時尿液,測定小鼠尿微量白蛋白的水平。Western blot檢測正常對照組(NC組)和DN小鼠Control組腎組織內(nèi)足細(xì)胞標(biāo)記物Desmin和Nephrin的蛋白表達(dá)水平。2. PTX3能夠減輕糖尿病腎病的腎損傷18 只 DN 小鼠分為三組,PTX3 組(n=6), Anti-PTX3 組(n=6)和 Control組(n=6 ),用免疫組化法檢測Desmin在三組小鼠腎組織中的表達(dá),Western blot檢測三組腎組織Nephrin和WT-1的蛋白水平。應(yīng)用流式細(xì)胞術(shù)(FCM)檢測三組腎組織中炎性細(xì)胞包括CD4+ T細(xì)胞、CD8+ T細(xì)胞、Ly6G+中性粒細(xì)胞和CD11b+巨噬細(xì)胞的數(shù)目。Western blot檢測三組腎組織炎癥因子包括IFN-γ、TNF-α、IL-4和IL-13的表達(dá)水平。結(jié)果1. STZ注射4周后糖尿病腎病模型組(Control組)血糖和尿微量白蛋白水平明顯高于正常對照組(NC組)(P0.05),Control組足細(xì)胞損傷標(biāo)記物Desmin蛋白表達(dá)水平顯著高于NC組,而正常足細(xì)胞標(biāo)記物Nephrin的蛋白水平顯著低于NC組(P0.05),說明糖尿病腎病小鼠模型成功建立。2.通過對DN小鼠三組(PTX3組、Anti-PTX3組、Control組)實驗結(jié)果的比較發(fā)現(xiàn),PTX3干預(yù)糖尿病腎病小鼠4周后,尿微量白蛋白定量明顯低于干預(yù)前(P0.05),在同期對照比較中,PTX3組尿微量白蛋白定量明顯低于Control組(P0.05); Desmin在PTX3組小鼠腎組織中的表達(dá)減少,Nephrin和WT-1的蛋白水平顯著高于Control組(P0.05),而Anti-PTX3組則顯示出相反的結(jié)果,加重了 DN的腎損傷。3. PTX3組腎組織中浸潤的炎性細(xì)胞包括CD4+ T細(xì)胞、CD8+ T細(xì)胞、Ly6G+中性粒細(xì)胞和CD11b+巨噬細(xì)胞的數(shù)目明顯少于Control組(P0.05),PTX3能夠上調(diào)抑炎性因子IL-4和IL-13,下調(diào)促炎性因子IFN-γ、TNF-α的表達(dá)(P0.05),說明PTX3能夠抑制促炎性免疫反應(yīng)。結(jié)論1. PTX3可以降低STZ誘導(dǎo)的糖尿病腎病小鼠尿微量白蛋白定量,具有穩(wěn)定足細(xì)胞結(jié)構(gòu)、減少足細(xì)胞損傷的作用,從而減輕糖尿病腎病的腎損傷。2.PTX3能夠減少糖尿病腎病小鼠腎組織中炎性細(xì)胞浸潤,上調(diào)抑炎性因子IL-4和IL-13,下調(diào)促炎性細(xì)胞因子IFN-γ、TNF-α的表達(dá),減輕腎組織的炎性損傷。研究背景及目的糖尿病腎病的發(fā)病機制尚不明確,高血糖、高血脂、高血壓等多種因素參與糖尿病腎病的發(fā)生與發(fā)展,這些因素誘導(dǎo)多種炎性介質(zhì)分泌,促進(jìn)炎性細(xì)胞聚集導(dǎo)致DN出現(xiàn)免疫損傷。因此多種炎癥因子和免疫細(xì)胞參與DN的免疫損傷,這是目前一致認(rèn)可的DN發(fā)病機制。DN早期,巨噬細(xì)胞作為最主要的炎性細(xì)胞浸潤在腎小球和腎間質(zhì)中,由于具有極強的異質(zhì)性,能夠在不同環(huán)境誘導(dǎo)下分化為不同表型的亞群,從而發(fā)揮不同的功能。Th1細(xì)胞因子IFN-γ、TNF-α可以刺激巨噬細(xì)胞向M1型分化(經(jīng)典活化型),M1主要表達(dá)iNOS、CD16/32、IL-12及TNF-a等促炎因子,主要發(fā)揮抗原提呈和免疫炎癥作用。Th2分泌IL-4和IL-13可以誘導(dǎo)巨噬細(xì)胞向M2型分化(替代活化型),M2高表達(dá)CD206、Arg-1及IL-10等分子,表現(xiàn)為抗炎活性,有很強的組織修復(fù)能力。臨床及動物實驗均顯示在糖尿病組織損傷部位存在以M1型巨噬細(xì)胞為主。在一定條件下,M1和M2亞型可相互轉(zhuǎn)換。我們第一部分實驗結(jié)果顯示PTX3能夠減少活性炎性細(xì)胞的浸潤,下調(diào)促炎性因子IFN-γ、TNF-α和上調(diào)抑炎性因子IL-4和IL-13的表達(dá),從而減少腎臟促炎性免疫反應(yīng),減輕糖尿病腎病的腎損傷。而IL-4和1L-13可以誘導(dǎo)巨噬細(xì)胞向M2型分化,推測PTX3可能具有調(diào)節(jié)巨噬細(xì)胞M1/M2動態(tài)平衡,促進(jìn)巨噬細(xì)胞向M2型分化,減少炎癥損傷的功能。因此本研究第二部分通過體內(nèi)和體外實驗研究PTX3是否能夠抑制M1型巨噬細(xì)胞表達(dá),促進(jìn)巨噬細(xì)胞向M2型轉(zhuǎn)化,進(jìn)一步說明PTX3通過促進(jìn)M2型巨噬細(xì)胞的分化減輕糖尿病腎病的腎損傷。材料與方法1.為研究PTX3是否影響巨噬細(xì)胞的極化作用,分別從DN小鼠模型和體外RAW264.7細(xì)胞培養(yǎng)進(jìn)行研究。利用本研究第一部分中三組DN小鼠(Control組、PTX3組和Anti-PTX3組)的腎臟取材標(biāo)本,Western blot檢測M1型巨噬細(xì)胞表型標(biāo)記物iNOS、CD16/32和M2型巨噬細(xì)胞表型標(biāo)記物CD206、Arg-1蛋白水平的變化,流式細(xì)胞術(shù)(Flow Cytometry,FCM)檢測M1型和M2型巨噬細(xì)胞的數(shù)目。2.小鼠單核巨噬細(xì)胞株RAW264.7用RPMI 1640培養(yǎng)基培養(yǎng),含10%FBS、青霉素100u/mL和鏈霉素100u/mL。采用高糖(右旋葡萄糖)濃度依賴性(11.1mM,20mM,30mM,35mM)以及時間依賴性(0h,6h,12h,24h,48h)剌激RAW264.7細(xì)胞株。用酶活性法檢測巨噬細(xì)胞活化表型標(biāo)志物iNOS的活性。Recombinant PTX3 (200ng/ml)干預(yù)高糖(30mM)組 RAW264.7 細(xì)胞,預(yù)孵育 12小時,Trizol法提取細(xì)胞RNA,采用RT-PCR技術(shù)檢測M1型巨噬細(xì)胞表型標(biāo)記物iNOS、CD16/32和M2型巨噬細(xì)胞表型標(biāo)記物CD206、Arg-1 mRNA的變化。結(jié)果1.與DN小鼠Control組相比,M1型巨噬細(xì)胞表型標(biāo)記物iNOS、CD16/32的蛋白水平在PTX3組中表達(dá)明顯增多而M2型標(biāo)記物CD206、Arg-1蛋白水平則顯著減少(P0.05),通過流式細(xì)胞術(shù)檢測M1型和M2型巨噬細(xì)胞的數(shù)目發(fā)現(xiàn),PTX3組M2型巨噬細(xì)胞的數(shù)目明顯多于M1型(P0.05),而Anti-PTX3組則顯示出相反的結(jié)果,說明PTX3可以促使DN小鼠腎組織的巨噬細(xì)胞由M1型向M2型轉(zhuǎn)化。2.高糖環(huán)境下能夠刺激RAW264.7的iNOS活性增強,呈濃度依賴性上升。其中,30mM高糖組刺激RAW264.7表達(dá)iNOS活性達(dá)最大值(48.1±6.6 U/mgprot,P0.05)。高糖時間依賴性刺激RAW264.7,高糖組從0至12h產(chǎn)生iNOS活性隨時間延長表達(dá)逐漸增加,呈時間依賴性。高糖刺激RAW264.7達(dá)12h時iNOS活性達(dá)最大值(44.6±10.7U/mgrot,P0.05)。高糖(30mM,121h)刺激M1型標(biāo)記物iNOS、CD16/32 mRNA 表達(dá)增加(P0.05),M2 型標(biāo)記物 CD206、Arg-1 mRNA表達(dá)下降(P0.05)。高糖(30mM)+ PTX3干預(yù)后,M1型標(biāo)記物iNOS、CD16/32 mRNA 表達(dá)下降(P0.05),M2 型標(biāo)記物 CD206、Arg-1 mRNA 表達(dá)增加(P0.05),說明高糖環(huán)境可以促使巨噬細(xì)胞向M1型活化,PTX3可以促使高糖環(huán)境下的RAW264.7細(xì)胞由M1型向M2型轉(zhuǎn)化。結(jié)論1. PTX3在體內(nèi)和體外實驗中均促使巨噬細(xì)胞由M1型向M2型轉(zhuǎn)化,達(dá)到減輕糖尿病腎病的腎損傷作用。2.高糖促進(jìn)RAW264.7細(xì)胞以時間和濃度依賴性表達(dá)iNOS活力,促使巨噬細(xì)胞向M1型轉(zhuǎn)化。
[Abstract]:Background and objective diabetes is a global disease. The International Diabetes Association data shows that the prevalence of diabetes is on the rise around the world, the prevalence rate is 8.8%, the number of people with diabetes in China is 109 million, the world is the first, and the rate of growth is very fast. About 1/3 of the patients develop into diabetes. Diabetic nephropathy (DN), DN is a kind of microvascular disease, which is one of the causes of death and disability, and is also the main cause of end-stage renal disease. Therefore, further research on the pathogenesis and development mechanism of diabetic nephropathy and the search for new therapeutic targets and treatment strategies are particularly important for the pathogenesis of.DN, which is not clear and high. Many factors such as blood sugar, hyperlipidemia and hypertension are involved in the development and development of diabetic nephropathy. These factors induce the secretion of various inflammatory mediators, promote inflammatory cell aggregation and lead to DN immune damage. Therefore, the activation of the immune system and the state of microinflammation are the consistent recognized pathogenesis of DN. Positive five polyprotein 3 (PTX3) is a kind of anti - C- CRP and serum amyloid A (SAP) belong to the acute inflammatory proteins belonging to the positive five polyprotein superfamily, which are secreted or synthesized by a variety of inflammatory immune cells such as neutrophils, macrophages, dendritic cells, and endothelial cells..CRP and SAP belong to the short chain positive five egg white, and PTX3 belongs to the long chain positive five protein, in a variety of inflammatory phases. Related diseases, such as microbial infection, autoimmune diseases, and atherosclerosis, play an important role. It can play a role of modulating hormone and regulating inflammation through pattern recognition, activating complement and other mechanisms. In acute and chronic infectious diseases, PTX3 and CRP can be used as a marker to increase rapidly in the blood and in some aseptic inflammation. Recently, some clinical studies have shown that elevated plasma PTX3 levels have a negative correlation with body mass index (BMI) related to cardiovascular disease and chronic renal disease (CKD), suggesting that PTX3 may play a role in obesity and metabolic syndrome. Recent studies have shown that AbuSemanN, and so on. The decrease of plasma PTX3 level is associated with type 2 diabetes and diabetic nephropathy. However, the current study is focused only on the elevation of endogenous PTX-3 levels or the relationship between silence and other diseases. There are few studies on the role of PTX3 therapy. Only sporadic studies have found that PTX3 can effectively prevent cytomegalovirus infection and reduce lung music. Fungal infection, lower mortality of mice model of sepsis. In acute myocardial infarction model, the role of protecting the heart, and the possible anti atherosclerotic related.Lech M studies in PTX3 have found that endogenous or exogenous PTX3 can reduce acute and chronic renal injury after ischemia reperfusion in mice. Based on the above background, this study The first part is to investigate whether PTX3 has the effect of reducing renal injury in diabetic nephropathy. Materials and methods 1. diabetic nephropathy (DN) model, 24 8-12 weeks male C57BL/6 mice were established, 6 normal mice were fed as normal control group (group NC) and.18 mice were injected with streptozotocin STZ (50mg/kg) for 5 days. Blood glucose and urine eggs were regularly detected. After 4 weeks of white.STZ injection, the model of DN mice was successfully modeled and divided into three groups, group PTX3 (n=6), DN mice were injected Recombinant PTX3 (0.5 mg/kg) after successful modeling, once a day for 4 weeks; Anti-PTX3 group (n=6) was a neutralization endogenous PTX3, and the anti rat PTX3 monoclonal antibody was injected intraperitoneally after the modeling was successful. Use PTX3 mAb, 0.2 mg/kg) was injected once a day for 4 weeks; group Control (n=6) was the control group of diabetic nephropathy mice, and the same dose of buffer solution was intraperitoneally injected. All mice were killed after 4 weeks (i.e. 8 weeks of STZ administration). The serum creatinine and 24 hours urine were measured before the intervention (STZ administration 4 weeks) and the dry prognosis (STZ for 8 weeks). The level of.Western blot in urine microalbuminuria was determined in the normal control group (group NC) and the protein expression level of Desmin and Nephrin in the renal tissue of Control group of Control group of DN mice,.2. PTX3 could reduce the renal injury of diabetic nephropathy, 18 DN mice were divided into three groups, PTX3 group (n), Immunohistochemistry was used to detect the expression of Desmin in the renal tissue of three groups of mice. Western blot was used to detect the protein levels of Nephrin and WT-1 in the three groups of renal tissues. The flow cytometry (FCM) was used to detect the inflammatory cells in the three groups of renal tissues including CD4+ T cells, CD8+ T cells, Ly6G+ neutrophils and CD11b+ macrophages, and three groups of kidneys were detected. Tissue inflammatory factors included the expression level of IFN- gamma, TNF- alpha, IL-4 and IL-13. Results after 4 weeks of 1. STZ injection, the levels of blood glucose and urine microalbuminuria in the diabetic nephropathy model group (group Control) were significantly higher than those in the normal control group (NC group) (P0.05). The expression of Desmin protein in the Control group of foot cell damage markers was significantly higher than that in the NC group, and the normal podocyte markers were significantly higher than those in the group Control group. The protein level of Nephrin was significantly lower than that of group NC (P0.05), indicating that the mice model of diabetic nephropathy successfully established.2. through the comparison of the experimental results of three groups of DN mice (group PTX3, Anti-PTX3 group, Control group), and it was found that the amount of urine albumin in urine was significantly lower than that before intervention (P0.05) after 4 weeks in diabetic nephropathy mice (P0.05). The amount of urine microalbuminuria in group PTX3 was significantly lower than that in group Control (P0.05), and the expression of Desmin in the renal tissue of PTX3 mice decreased, and the protein level of Nephrin and WT-1 was significantly higher than that in Control group (P0.05), while the Anti-PTX3 group showed the opposite result, which aggravated the DN renal injury. The number of cells, CD8+ T cells, Ly6G+ neutrophils and CD11b+ macrophages was significantly less than that of group Control (P0.05). PTX3 could up regulate the anti inflammatory factors IL-4 and IL-13, down regulated the proinflammatory factor IFN- gamma, TNF- alpha expression (P0.05), indicating that it could inhibit the anti inflammatory immune response. Conclusion 1. can reduce the induced diabetic nephropathy mice. Urine microalbuminuria, which can stabilize the podocyte structure, reduce the effect of foot cell injury, and reduce the renal injury of diabetic nephropathy,.2.PTX3 can reduce inflammatory cell infiltration in renal tissue of diabetic nephropathy mice, increase anti inflammatory factors IL-4 and IL-13, down regulate the expression of proinflammatory cytokines IFN- gamma, TNF- alpha, and reduce inflammation of kidney tissue. The pathogenesis of diabetic nephropathy is not clear. Many factors such as hyperglycemia, hyperlipidemia, hypertension and other factors are involved in the development and development of diabetic nephropathy. These factors induce various inflammatory mediators to secrete and promote inflammatory cell aggregation to lead to DN immune injury. So a variety of inflammatory factors and immune cells are involved in DN The immune injury, which is the unanimous DN pathogenesis in the early stage of.DN, is the most important inflammatory cell infiltrating in the glomeruli and the renal interstitium. Because of its strong heterogeneity, it can differentiate into subgroups of different phenotypes in different environments, thus causing different functional.Th1 cytokines, IFN- gamma, and TNF- alpha. The macrophages were stimulated to differentiate into M1 type (classical activation type), and M1 mainly expressed iNOS, CD16/32, IL-12 and TNF-a, which mainly played the antigen presentation and immune inflammation,.Th2 secreted IL-4 and IL-13, which could induce macrophage to differentiate into M2 type (instead of activating type). The strong tissue repair ability. Clinical and animal experiments showed that M1 type macrophages were dominant in the site of diabetic tissue injury. Under certain conditions, M1 and M2 subtypes could be converted to each other. Our first experimental results showed that PTX3 could reduce the infiltration of active inflammatory cells, the lower modulation of inflammatory factors IFN- gamma, TNF- alpha and up regulation of anti inflammatory properties. The expression of factor IL-4 and IL-13 reduces renal proinflammatory response and reduces renal damage in diabetic nephropathy. IL-4 and 1L-13 can induce macrophage to differentiate into M2 type. It is presumed that PTX3 may have the function of regulating the dynamic balance of M1/M2 in macrophages, promoting the differentiation of macrophages into M2 type, and reducing the function of inflammatory damage. Therefore, second parts of this study were studied. Whether PTX3 can inhibit the expression of M1 type macrophages and promote the transformation of macrophage to M2 type through the experiment in vitro and in vitro, further illustrates that PTX3 can reduce the renal damage of diabetic nephropathy by promoting the differentiation of M2 type macrophages. Material and method 1. is to study whether PTX3 affects the polarization of macrophage cells, from the DN mouse model, respectively. In the first part of this study, three groups of DN mice (group Control, PTX3 and Anti-PTX3) were used in the study. Western blot was used to detect the phenotypic markers of M1 type macrophages, iNOS, CD16/32 and M2 type macrophages, the changes in protein level, and flow cytometry. Etry, FCM) detection of the number of M1 and M2 macrophages in the.2. mouse mononuclear macrophage strain RAW264.7 with RPMI 1640 culture medium, containing 10%FBS, penicillin 100u/mL and streptomycin 100u/mL. using high glucose concentration dependent (11.1mM, 20mM, disposable) stimulant cell strain. Activity method detected active.Recombinant PTX3 (200ng/ml) of macrophage activation phenotypic marker iNOS (200ng/ml) to interfere with high glucose (30mM) group RAW264.7 cells, incubated for 12 hours, Trizol method was used to extract cell RNA, and RT-PCR technique was used to detect phenotypic markers of M1 macrophage, CD16/32 and phenotype markers of macrophages were changed. Results 1. compared with the Control group of DN mice, the phenotype markers of M1 macrophages were iNOS, the protein level of CD16/32 increased significantly in the PTX3 group and the M2 type marker CD206, and the Arg-1 protein level decreased significantly (P0.05). The number of M1 and M2 type macrophages was detected by flow cytometry. More than type M1 (P0.05), and Anti-PTX3 group showed the opposite results, indicating that PTX3 could promote the increase of iNOS activity of RAW264.7 in DN mouse kidney tissue from M1 to M2 type.2. high sugar environment, which increased in a concentration dependent manner. The maximum value of 30mM high glucose group stimulated RAW264.7 expression to reach the maximum value (48.1 + 6.6). Rot, P0.05). High glucose time dependent stimulation of RAW264.7, the activity of iNOS in high glucose group increased from 0 to 12h and increased with time. The activity of high glucose was time dependent. The activity of iNOS was maximum (44.6 + 10.7U/mgrot, P0.05) when high glucose stimulated RAW264.7 (12h). CD206, Arg-1 mRNA expression decreased (P0.05). High sugar (30mM) + PTX3 dry prognosis, M1 type iNOS, CD16/32 mRNA expression decreased (P0.05). Conclusion 1. PTX3 in both in vivo and in vitro stimulated the transformation of macrophages from M1 type to M2 type to alleviate the renal injury of diabetic nephropathy, and.2. high glucose could promote RAW264.7 cells to express iNOS activity in time and concentration dependent manner, and promote the transformation of macrophages into M1 type.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R587.2;R692.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;Effects of mycophenolate mofetil,valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats[J];Chinese Medical Journal;2007年11期

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本文編號：1942504