筋骨草总黄酮治疗系膜增生性肾小球肾炎的实验研究及其机制探讨
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摘要
第一章理论研究
系膜增生性肾小球肾炎(MsPGN)是肾小球疾病中最为常见的病理类型,弥漫性肾小球系膜细胞(GMC)增生和/或不同程度细胞外基质(ECM)增多是其主要的病理学特征。其发病机理至今尚未完全阐明,目前认为免疫学机制是该病的始发因素,但其本身对肾脏的直接损伤是有限的,而在此基础上激活的一系列炎症介导系统是造成肾小球损伤和产生临床表现的直接原因。鉴于此原因,MsPGN出现大量蛋白尿等表现时,应用糖皮质激素、免疫抑制剂仍是目前主要的治疗手段,但病情往往易迁延、反复,且存在不同程度的副作用。此外,由于众多炎性细胞因子构成的复杂网络及过度释放时形成的瀑布效应,使得针对单一炎性细胞因子的对抗措施在临床上难以取得预期的疗效,而多种抗体的联合搭配使用又显得不切实际。基于NF-κB对炎性细胞因子基因表达起着中心调控作用,因此,通过抑制上游转导通路NF-κB活化的抗炎治疗逐渐成为肾脏疾病治疗的新靶点。近年来随着中医药的深入研究和中医对MsPGN的病因和发病机制的更进一步认识,中医药治疗MsPGN取得了一定进展,并显示出中医药治疗该病有一定优势及潜能。中医学认为湿热在MsPGN发病过程中起着非常重要的作用,是促进肾脏病理损害,加速肾功能恶化的重要因素。处理好湿热证,对于控制病情,保护肾功能都很有意义。筋骨草为福建常用中草药,性味苦寒,具有清热燥湿的作用,其有效成分黄酮类化合物木犀草素具有抗炎、抑制变态反应、抗增殖等活性。根据上述理论,我们推测筋骨草总黄酮(TFA)可能对肾小球肾炎具有治疗作用。为此,我们设计了本研究。经过检索查新,本研究目前无相关报道。
第二章实验研究
目的：探讨TFA对MsPGN模型大鼠的治疗作用及可能的作用机制。体外观察TFA含药血清对LPS诱导的GMC增殖、ECM分泌及NF-κB/IκB信号转导途径的干预作用,旨在从细胞生物学及分子水平探讨TFA治疗MsPGN的可能机制,为其进一步开发利用提供一定的实验依据。
方法：体内研究：采用改良慢性血清病法复制MsPGN大鼠模型,造模第5w末将尿蛋白阳性者随机分为模型对照组、雷公藤多苷组(0.018g·kg-1·day-1, TPG组)、TFA高剂量组(2.16g·kg-1·day-1)、中剂量组(1.08g·kg-1·day-1)、低剂量组(0.54g·kg-1·day-1),另设正常对照组。于造模第6w开始给药,连续6w后,检测各组大鼠24h尿蛋白定量和血生化指标；采用化学比色法分别检测各组大鼠血清MDA含量及其调节酶SOD活性的变化；采用放射免疫分析法检测各组大鼠血清IL-1、TNF-κ的浓度；采用ELISA法检测大鼠血清TGF-β1的表达水平；采用免疫组化法检测各组大鼠肾小球中NF-κB p65的表达情况。光镜下观察各组大鼠肾小球系膜区情况及GMC和ECM积聚情况。体外研究：(1)大鼠每日灌胃2次,连续3d,末次给药1h后制备实验血清；(2)采用台盼蓝染色排斥法检测TFA不同浓度含药血清对细胞活力的影响。(3)据细胞活力实验和预实验结果确定TFA含药血清浓度,将同步于静止期GMC分为以下各组：①正常对照组：加入10%正常大鼠血清；②LPS组：加入LPS10μg/ml和10%正常大鼠血清；③10%TFA含药血清组：加入LPS10μg/ml+10%TFA含药血清；④5%TFA含药血清组：加入LPS10μg/ml+5%TFA含药血清；⑤2.5%TFA含药血清组：加入LPS10μg/ml+2.5%TFA含药血清。(4)干预24h、48h后,用MTT法检测GMC的增殖情况；采用ELISA法检测细胞上清液中FN、Col-Ⅳ、MCP-1的表达情况。对干预48h的GMC采用流式细胞术检测细胞周期和RT-PCR检测MMP-9mRNA、NF-κB mRNA和IκB mRNA的表达水平。
结果：体内研究：(1)给药6w后,各治疗组较模型对照组尿蛋白明显降低(P<0.01或P<0.05),而TFA高、中剂量组尿蛋白含量虽低于TPG组,但无统计学意义(P>0.05)。(2)与模型对照组相比,TFA干预性治疗后TP明显升高,而TG、Tch、BUN、Scr明显降低,(P<0.01或P<0.05)。(3)肾组织病理形态学观察模型对照组GMC明显增殖,基质增多、系膜区明显增宽、毛细血管受压变窄或消失,半定量分析结果显示模型对照组系膜区面积/毛细血管丛面积比值较正常对照组显著升高(P<0.01)；TFA干预性治疗后上述病理改变明显减轻(P<0.01或P<0.05)。(4)TFA干预性治疗后与模型对照组相比SOD活力明显提高,MDA、IL-1、TNF-α、TGF-β1、肾小球NF-κB p65的表达则明显降低(P<0.05或P<0.01),且NF-κB核移位明显受到抑制。(5)相关性分析显示,NF-κB p65与IL-1、TNF-α、TGF-β1均呈显著正相关(r=0.566、r=0.669、r=0.598,P<0.05)。体外研究：(1)20%、10%、5%和2.5%浓度TFA含药血清组24和48h细胞活力均达95%以上,无明显细胞毒性。(2)TFA含药血清干预24h、48h后LPS诱导GMC增殖水平、细胞上清液中FN、Col-Ⅳ、MCP-1表达较LPS组明显降低(P<0.05或P<0.01)。干预48h后,与LPS组相比处于G1期的细胞比例、MMP-9 mRNA和IκB mRNA相对表达量明显增高,而S期细胞比例、NF-κB mRNA相对表达量均明显降低(P<0.05或P<0.01)。(3)相关性分析显示NF-κB mRNA与IκB mRNA、MMP-9 mRNA (r=-0.724、r=-0.781, P<0.05),均呈显著负相关。
结论：首次证实,TFA能降低MsPGN大鼠蛋白尿,保护肾功能,抑制GMC增殖及ECM积集,减轻肾小球损伤,提示TFA对MsPGN有一定治疗作用,其作用可能与TFA抗氧化作用,调控NF-κB/IκB信号转导途径,继而调控细胞周期和炎症因子(IL-1、TNF-α、TGF-β1、MMP-9、MCP-1)的表达有关。
Part 1:Theoretical research
Mesangial proliferative glomerulonephritis (MsPGN) turns out to be the most common clinic type in renal glomerular disease, those main pathological features were hyperplasia of glomerular mesangial cell (GMC) as well as more or less increasements of extracellular matrix (ECM) in disease progression. But up till now, there have been no integrate clarification about its pathomechanism. Immunopathogenesis has been validated as a matter of its initial pathogenic factor which has limited direct damage to the kidney, but will activate a series of inflammation-mediated system which will resort severe damage to glomerular and make influences on clinical manifestations. Based on these factors, glucocorticoid and other immunosuppressive agents are now widely used in treating massive proteinuria or any other kind of symptoms, offen brings about side-effects and almost can't inhibit disease progression. As it is well-known that inflammatory cytokines constitute a complicated network and meantime the over-released leads to the so-called "Casada effect", so it is hard to achieve the prospective effects in clinic treatment with single anti-inflamatory cytokines and unpractical with multiple antibodies. Based on the studies about NF-κB who played a central regulatory role in gene expression of inflammatory cytokines, NF-κB inhibitation is now considered to be a new target in anti-inflamatory area. Nowdays, with the further study of Chinese herbs on etiological factor and pathogenesis of MsPGN, people have made prominent advancements and large potential conquering this disease. Chinese pathogenesis for MsPGN is mostly focused on dampness-heat which we believe will acclerate disease progression especially in renal function damage. To dispel dampness-heat is to control the disease, to protect renal function. Ajuga is a local familiar Chinese Herb in fujian province with bittery tasted and cold in nature, which can clear heat and dispel dampness according to TCM theory. As active ingredients, Luteolin has function of anti-inflammatory, inhibiting allergical reaction, anti-proliferation, etc. Based on these TCM theory and current research, we hypothesis that total flavonoids of Ajuga (TFA) has positive treatmental effects on glomerulonephritis. On account of this idea, we worked out the research under the background of no relevant report in Via index or novelty retrieval.
Part2:Experimental Research
Objective:To observe the effect of total flavonoids of Ajuga (TFA) on Rats with mesangial proliferative glomerulonephritis (MsPGN) and its therapeutic mechanism.
Methods:In vivo, we established the improved animal model of chronic serum sickness MsPGN. The model rats with positive urinary protein were randomly divided into the model control group, the tripterygium wilfordii polycoride group (TPG group, 0.018g·kg-1·day-1), the TFA high-dosage group (2.16g·kg-1·day-1), the TFA mid-dosage group (1.08g·kg-1·day-1), and the TFA low-dosage group (0.54g·kg-1·day-1), with the normal rats as control group. After six weeks, 24 h urinary protein, blood biochemistry were detected. Rats Mesangium, GMC and ECM accumulation were observated under the light microscope. The content of MDA and SOD activity was detected by chemical colorimetric assay, the concentration of IL-1, TNF-αby radio immunoassay, the expression of TGF-β1 by ELISA, and the expression of NF-κB p65 in rats nephridial tissue with immunohistochemistry.
In vitro, TFA containing serum was prepared, its experimental concentration was determined according to the cell viability and pre-test results. The GMC synchronized in the quiescent culture were divided into following groups:①normal control group (adding 10% normal rat serum),②LPS group (adding LPS 10μg/ml and 10% normal rat serum),③10% TFA groups (adding 10μg/ml LPS and 10% concentration of TFA-containing serum),④5% TFA groups (adding lOμg/ml LPS and 5% concentration of TFA-containing serum),⑤2.5% TFA groups (adding 10μg/ml LPS and 2.5% concentration of TFA-containing serum). After confounding factor added, the cells and medium were collected in 24h and 48h to detect the proliferation of GMC by MTT assay. The expression of FN, Col-IV, and MCP-1 were observated by using ELISA. Mitotic cycle of GMC were detected by flow cytometry in 48h, and RT-PCR was used to detect the expression of MMP-9mRNA, NF-κB mRNA and IκB mRNA.
Results:In vivo, the excretion of urine protein in TFA groups and TPG group were more significantly decreased than in model control group (P<0.01 or P<0.05). GMC in model group increased significantly, mesangial region became obviously widen, groundsubstance increased, the capillaries were pressed into narrowing or disappearing, those pathomorphological changed in TFA groups dramatically lessen (P<0.01 or P<0.05). There were no statistics difference in urine protein excretion and pathomorphological change among TFA high-dosage, mid-dosage groups and TWG group (P>0.05). SOD activity in TFA groups were obviously higher than model control group, the expression of MDA, IL-1, TNF-α, TGF-β1 and NF-κB p65 were obviously decreased (P<0.05 or P<0.01), and nuclear translocation of NF-κB was significantly inhibited. The effect of increasing SOD activity and decreasing the content of MDA in TFA mid-dosage group were better than TPG group (P<0.05). The relative analysis shows the expression of NF-κB p65 was significantly positive correlation with the expression of Serum IL-1, TNF-α, TGF-β1 (r=0.566, P<0.05;r=0.669, P<0.05;r=0.598,P<0.05), and was significantly negative correlation with SOD activity (r=-0.825, P＜0.01).
In vitro, After 24h and 48h, the cell viability had reached more than 95% in 20%,10%,5% and 2.5% concentration of drug-containing serum group, respectively, with no evident cell toxic action. The proliferation of GMC and the expression of FN, Col-Ⅳ, MCP-1 in TFA-containing serum group at 24h and 48h were obviously lower than those in LPS group (P<0.05 or P<0.01). When acting on GMC for 48h, the percentage of GMC in G1 phases, the expression of MMP-9 mRNA and IκB mRNA in TFA-containing serum group were obviously higher than those in LPS group, while the percentage of GMC in S phases and the expression of IκB mRNA were obviously lower (P<0.05 or P<0.01). The relative analysis showed that the express of NF-κB mRNA was significant negative correlation with the expression of IκB mRNA.
Conclusion:The research indicated that TFA had a certain therapeutical effect on MsPGN, including decreasing urine protein excretion; protecting kidney function, inversing the MsPGN pathomorphological change. Its therapeutic mechanism might be related to resist oxidative stress, regulate NF-κB/IκB signal transduction, and successively regulate the expression of cell cycle and inflammatory factors (IL-1,TNF-α, TGF-β1, MMP-9, MCP-1).
系膜增生性肾小球肾炎(MsPGN)是肾小球疾病中最为常见的病理类型,弥漫性肾小球系膜细胞(GMC)增生和/或不同程度细胞外基质(ECM)增多是其主要的病理学特征。其发病机理至今尚未完全阐明,目前认为免疫学机制是该病的始发因素,但其本身对肾脏的直接损伤是有限的,而在此基础上激活的一系列炎症介导系统是造成肾小球损伤和产生临床表现的直接原因。鉴于此原因,MsPGN出现大量蛋白尿等表现时,应用糖皮质激素、免疫抑制剂仍是目前主要的治疗手段,但病情往往易迁延、反复,且存在不同程度的副作用。此外,由于众多炎性细胞因子构成的复杂网络及过度释放时形成的瀑布效应,使得针对单一炎性细胞因子的对抗措施在临床上难以取得预期的疗效,而多种抗体的联合搭配使用又显得不切实际。基于NF-κB对炎性细胞因子基因表达起着中心调控作用,因此,通过抑制上游转导通路NF-κB活化的抗炎治疗逐渐成为肾脏疾病治疗的新靶点。近年来随着中医药的深入研究和中医对MsPGN的病因和发病机制的更进一步认识,中医药治疗MsPGN取得了一定进展,并显示出中医药治疗该病有一定优势及潜能。中医学认为湿热在MsPGN发病过程中起着非常重要的作用,是促进肾脏病理损害,加速肾功能恶化的重要因素。处理好湿热证,对于控制病情,保护肾功能都很有意义。筋骨草为福建常用中草药,性味苦寒,具有清热燥湿的作用,其有效成分黄酮类化合物木犀草素具有抗炎、抑制变态反应、抗增殖等活性。根据上述理论,我们推测筋骨草总黄酮(TFA)可能对肾小球肾炎具有治疗作用。为此,我们设计了本研究。经过检索查新,本研究目前无相关报道。
第二章实验研究
目的：探讨TFA对MsPGN模型大鼠的治疗作用及可能的作用机制。体外观察TFA含药血清对LPS诱导的GMC增殖、ECM分泌及NF-κB/IκB信号转导途径的干预作用,旨在从细胞生物学及分子水平探讨TFA治疗MsPGN的可能机制,为其进一步开发利用提供一定的实验依据。
方法：体内研究：采用改良慢性血清病法复制MsPGN大鼠模型,造模第5w末将尿蛋白阳性者随机分为模型对照组、雷公藤多苷组(0.018g·kg-1·day-1, TPG组)、TFA高剂量组(2.16g·kg-1·day-1)、中剂量组(1.08g·kg-1·day-1)、低剂量组(0.54g·kg-1·day-1),另设正常对照组。于造模第6w开始给药,连续6w后,检测各组大鼠24h尿蛋白定量和血生化指标；采用化学比色法分别检测各组大鼠血清MDA含量及其调节酶SOD活性的变化；采用放射免疫分析法检测各组大鼠血清IL-1、TNF-κ的浓度；采用ELISA法检测大鼠血清TGF-β1的表达水平；采用免疫组化法检测各组大鼠肾小球中NF-κB p65的表达情况。光镜下观察各组大鼠肾小球系膜区情况及GMC和ECM积聚情况。体外研究：(1)大鼠每日灌胃2次,连续3d,末次给药1h后制备实验血清；(2)采用台盼蓝染色排斥法检测TFA不同浓度含药血清对细胞活力的影响。(3)据细胞活力实验和预实验结果确定TFA含药血清浓度,将同步于静止期GMC分为以下各组：①正常对照组：加入10%正常大鼠血清；②LPS组：加入LPS10μg/ml和10%正常大鼠血清；③10%TFA含药血清组：加入LPS10μg/ml+10%TFA含药血清；④5%TFA含药血清组：加入LPS10μg/ml+5%TFA含药血清；⑤2.5%TFA含药血清组：加入LPS10μg/ml+2.5%TFA含药血清。(4)干预24h、48h后,用MTT法检测GMC的增殖情况；采用ELISA法检测细胞上清液中FN、Col-Ⅳ、MCP-1的表达情况。对干预48h的GMC采用流式细胞术检测细胞周期和RT-PCR检测MMP-9mRNA、NF-κB mRNA和IκB mRNA的表达水平。
结果：体内研究：(1)给药6w后,各治疗组较模型对照组尿蛋白明显降低(P<0.01或P<0.05),而TFA高、中剂量组尿蛋白含量虽低于TPG组,但无统计学意义(P>0.05)。(2)与模型对照组相比,TFA干预性治疗后TP明显升高,而TG、Tch、BUN、Scr明显降低,(P<0.01或P<0.05)。(3)肾组织病理形态学观察模型对照组GMC明显增殖,基质增多、系膜区明显增宽、毛细血管受压变窄或消失,半定量分析结果显示模型对照组系膜区面积/毛细血管丛面积比值较正常对照组显著升高(P<0.01)；TFA干预性治疗后上述病理改变明显减轻(P<0.01或P<0.05)。(4)TFA干预性治疗后与模型对照组相比SOD活力明显提高,MDA、IL-1、TNF-α、TGF-β1、肾小球NF-κB p65的表达则明显降低(P<0.05或P<0.01),且NF-κB核移位明显受到抑制。(5)相关性分析显示,NF-κB p65与IL-1、TNF-α、TGF-β1均呈显著正相关(r=0.566、r=0.669、r=0.598,P<0.05)。体外研究：(1)20%、10%、5%和2.5%浓度TFA含药血清组24和48h细胞活力均达95%以上,无明显细胞毒性。(2)TFA含药血清干预24h、48h后LPS诱导GMC增殖水平、细胞上清液中FN、Col-Ⅳ、MCP-1表达较LPS组明显降低(P<0.05或P<0.01)。干预48h后,与LPS组相比处于G1期的细胞比例、MMP-9 mRNA和IκB mRNA相对表达量明显增高,而S期细胞比例、NF-κB mRNA相对表达量均明显降低(P<0.05或P<0.01)。(3)相关性分析显示NF-κB mRNA与IκB mRNA、MMP-9 mRNA (r=-0.724、r=-0.781, P<0.05),均呈显著负相关。
结论：首次证实,TFA能降低MsPGN大鼠蛋白尿,保护肾功能,抑制GMC增殖及ECM积集,减轻肾小球损伤,提示TFA对MsPGN有一定治疗作用,其作用可能与TFA抗氧化作用,调控NF-κB/IκB信号转导途径,继而调控细胞周期和炎症因子(IL-1、TNF-α、TGF-β1、MMP-9、MCP-1)的表达有关。
Part 1:Theoretical research
Mesangial proliferative glomerulonephritis (MsPGN) turns out to be the most common clinic type in renal glomerular disease, those main pathological features were hyperplasia of glomerular mesangial cell (GMC) as well as more or less increasements of extracellular matrix (ECM) in disease progression. But up till now, there have been no integrate clarification about its pathomechanism. Immunopathogenesis has been validated as a matter of its initial pathogenic factor which has limited direct damage to the kidney, but will activate a series of inflammation-mediated system which will resort severe damage to glomerular and make influences on clinical manifestations. Based on these factors, glucocorticoid and other immunosuppressive agents are now widely used in treating massive proteinuria or any other kind of symptoms, offen brings about side-effects and almost can't inhibit disease progression. As it is well-known that inflammatory cytokines constitute a complicated network and meantime the over-released leads to the so-called "Casada effect", so it is hard to achieve the prospective effects in clinic treatment with single anti-inflamatory cytokines and unpractical with multiple antibodies. Based on the studies about NF-κB who played a central regulatory role in gene expression of inflammatory cytokines, NF-κB inhibitation is now considered to be a new target in anti-inflamatory area. Nowdays, with the further study of Chinese herbs on etiological factor and pathogenesis of MsPGN, people have made prominent advancements and large potential conquering this disease. Chinese pathogenesis for MsPGN is mostly focused on dampness-heat which we believe will acclerate disease progression especially in renal function damage. To dispel dampness-heat is to control the disease, to protect renal function. Ajuga is a local familiar Chinese Herb in fujian province with bittery tasted and cold in nature, which can clear heat and dispel dampness according to TCM theory. As active ingredients, Luteolin has function of anti-inflammatory, inhibiting allergical reaction, anti-proliferation, etc. Based on these TCM theory and current research, we hypothesis that total flavonoids of Ajuga (TFA) has positive treatmental effects on glomerulonephritis. On account of this idea, we worked out the research under the background of no relevant report in Via index or novelty retrieval.
Part2:Experimental Research
Objective:To observe the effect of total flavonoids of Ajuga (TFA) on Rats with mesangial proliferative glomerulonephritis (MsPGN) and its therapeutic mechanism.
Methods:In vivo, we established the improved animal model of chronic serum sickness MsPGN. The model rats with positive urinary protein were randomly divided into the model control group, the tripterygium wilfordii polycoride group (TPG group, 0.018g·kg-1·day-1), the TFA high-dosage group (2.16g·kg-1·day-1), the TFA mid-dosage group (1.08g·kg-1·day-1), and the TFA low-dosage group (0.54g·kg-1·day-1), with the normal rats as control group. After six weeks, 24 h urinary protein, blood biochemistry were detected. Rats Mesangium, GMC and ECM accumulation were observated under the light microscope. The content of MDA and SOD activity was detected by chemical colorimetric assay, the concentration of IL-1, TNF-αby radio immunoassay, the expression of TGF-β1 by ELISA, and the expression of NF-κB p65 in rats nephridial tissue with immunohistochemistry.
In vitro, TFA containing serum was prepared, its experimental concentration was determined according to the cell viability and pre-test results. The GMC synchronized in the quiescent culture were divided into following groups:①normal control group (adding 10% normal rat serum),②LPS group (adding LPS 10μg/ml and 10% normal rat serum),③10% TFA groups (adding 10μg/ml LPS and 10% concentration of TFA-containing serum),④5% TFA groups (adding lOμg/ml LPS and 5% concentration of TFA-containing serum),⑤2.5% TFA groups (adding 10μg/ml LPS and 2.5% concentration of TFA-containing serum). After confounding factor added, the cells and medium were collected in 24h and 48h to detect the proliferation of GMC by MTT assay. The expression of FN, Col-IV, and MCP-1 were observated by using ELISA. Mitotic cycle of GMC were detected by flow cytometry in 48h, and RT-PCR was used to detect the expression of MMP-9mRNA, NF-κB mRNA and IκB mRNA.
Results:In vivo, the excretion of urine protein in TFA groups and TPG group were more significantly decreased than in model control group (P<0.01 or P<0.05). GMC in model group increased significantly, mesangial region became obviously widen, groundsubstance increased, the capillaries were pressed into narrowing or disappearing, those pathomorphological changed in TFA groups dramatically lessen (P<0.01 or P<0.05). There were no statistics difference in urine protein excretion and pathomorphological change among TFA high-dosage, mid-dosage groups and TWG group (P>0.05). SOD activity in TFA groups were obviously higher than model control group, the expression of MDA, IL-1, TNF-α, TGF-β1 and NF-κB p65 were obviously decreased (P<0.05 or P<0.01), and nuclear translocation of NF-κB was significantly inhibited. The effect of increasing SOD activity and decreasing the content of MDA in TFA mid-dosage group were better than TPG group (P<0.05). The relative analysis shows the expression of NF-κB p65 was significantly positive correlation with the expression of Serum IL-1, TNF-α, TGF-β1 (r=0.566, P<0.05;r=0.669, P<0.05;r=0.598,P<0.05), and was significantly negative correlation with SOD activity (r=-0.825, P＜0.01).
In vitro, After 24h and 48h, the cell viability had reached more than 95% in 20%,10%,5% and 2.5% concentration of drug-containing serum group, respectively, with no evident cell toxic action. The proliferation of GMC and the expression of FN, Col-Ⅳ, MCP-1 in TFA-containing serum group at 24h and 48h were obviously lower than those in LPS group (P<0.05 or P<0.01). When acting on GMC for 48h, the percentage of GMC in G1 phases, the expression of MMP-9 mRNA and IκB mRNA in TFA-containing serum group were obviously higher than those in LPS group, while the percentage of GMC in S phases and the expression of IκB mRNA were obviously lower (P<0.05 or P<0.01). The relative analysis showed that the express of NF-κB mRNA was significant negative correlation with the expression of IκB mRNA.
Conclusion:The research indicated that TFA had a certain therapeutical effect on MsPGN, including decreasing urine protein excretion; protecting kidney function, inversing the MsPGN pathomorphological change. Its therapeutic mechanism might be related to resist oxidative stress, regulate NF-κB/IκB signal transduction, and successively regulate the expression of cell cycle and inflammatory factors (IL-1,TNF-α, TGF-β1, MMP-9, MCP-1).
引文
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