Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions

Objective： The aim of this study was to investigate the effects of plumbagin （PL）, a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells. Methods： Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plum- bagin for 24 h. The effects of plumbagin on the migration and invasion were observed by a transwell method. The expressions of IL-1α, IL-1β, IL-6, IL-8, TGF-β, TNFα, MMP-2 and MMP-9 mRNA in MDA-MB-231SArfp cells were detected using Real-Time PCR. MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes. The activation of STAT3 was detected by western blot. Following this analysis, STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA, mRNA levels of IL-1α, TGF-β, MMP-2 and MMP-9 were then detected. Consequently, MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model. The mice were injected intra- peritoneally with plumbagin. Non-invasive in vivo monitoring, X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo. Results： The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1α TGF-β, MMP-2 and MMP-9. Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB-231SArfp cells. The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1α, TGF-β, MMP-2 and MMP-9. In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases, as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions. Conclusions： Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and by downregulation of IL-1α, TGF-β, MMP-2 and MMP-9.

Plumbagin Enhances TRAIL-mediated Apoptosis through Up-regulation of Death Receptor in Human Melanoma A375 Cells

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from plant. In this study, induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated. The cells were divided into four groups: control group, plumbagin group (plumbagin, 5 or 10 μmol/L), TRAIL group (TRAIL, 30 ng/mL) and plumbagin+TRAIL group (combined treatment group). The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that the apoptosis rate was 8.3% in TRAIL group, 10.35%–16.94% in plumbagin group and 52.39%–65.39% in combined treatment group, respectively, with the difference being significant between combined treatment group and plumbagin or TRAIL group (P<0.05 for each). Moreover, plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression. Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3, but not Caspase-8. These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.

In vitro inhibitory effects of plumbagin,the promising antimalarial candidate,on human cytochrome P450 enzymes

Objective:To investigate the propensity of plumbagin to inhibit the three isoforms of human cytochrome P450(CYP),ie.,CYP1A2,CYP2C19,and CYP3A4 using human liver microsomes in ritro.Methods:Inhibitory effects of plumbagin on the three human CYP isoformswere investigated using pooled human liver microsomes.Phenacetin O-deethylation,omeprazole hydroxylation and nifedipine oxidation were used as selective substrates for CYP1A2,CYP2C19 and CYP3A4 activities,respectively.Concentrations of paracetamol,5-hydroxyomeprazole,and oxidized nifedipine were determined in microsomal incubation mixture using high performance liquid chromatography.Results:Plumbagin showed significantinhibitory effects on all CYP isoforms.but with the most potent activity on CYP2C19-mediated omeprazole hydroxylation.The IC50(concentration that inhibits enzyme activity by 50%) values of plumbagin and nootkatone(selective inhibitor) for CYP2C19 were(0.78±0.01) and(27.31±0.66) μM,respectively.The inhibitory activities on CYP1 A2-mediated phenacetin O-deethylation and CYP3A4-mediated nifedipine oxidation were moderate.The IC_(50) values of plumbagin and-naphthoflavone(selective inhibitor) for CYP1A2 were(1.39±0.01) and(0.02±.0.36) μM,respectively.The corresponding IC_(50) values of plumbagin and ketoconazole(selective inhibitor) for CYP3A4 were(2.37+0.10) and(0.18±0.06) μM,respectively.Conclusions:Clinical relevance of the interference of human drug metabolizing enzymes should be aware of for further development scheme of plumbagin as antimalarial drug when used in combination with other antimalarial drugs which are metabolized by these CYP isoforms.

Inhibitory activities of plumbagin on cell migration and invasion and inducing activity on cholangiocarcinoma cell apoptosis

Objective: To investigate the cytotoxic, apoptotic and inhibitory activities on cell migration and invasion of plumbagin in the human cholangiocarcinoma(CCA) cell line(CL-6) in comparison with human embryonic fibroblast cell line(OUMS). Methods: Cytotoxicity activity was evaluated using MTT assay. Inhibitory effect on cell migration and invasion were investigated using label-free real-time cell analysis and QCM ECMatrix cell invasion chamber, respectively. Apoptotic activity was evaluated using flow cytometry and Cell Event? Caspase 3/7 assay. Results: Based on results of the cytotoxicity test in CL-6 cells, 50% inhibitory concentration(IC_(50), Mean±SD) values of plumbagin and the standard drug 5-fluorouracil were(24.00±3.33) and(1 036.00±137.77) μmol/L, respectively. The corresponding values for OUMS cells were(57.00±5.23) and(2 147.00±209.98) μmol/L, respectively. The selectivity index was 2.28. The inhibitory activities of plumbagin on cell migration and invasion were potent and concentration-dependent with IC_(50) of 25.0 μmol/L and complete inhibition at 25.0 μmol/L. Flow cytometry analysis showed that plumbagin at 12.5 μmol/L(half IC_(50)) induced CL-6 cell apoptosis(43.24% of control) through stimulation of caspase 3/7 activities. Complete cell apoptosis was observed at 12.5 μmol/L. Conclusions: The cytotoxic activity and inhibition of migration and invasion including apoptosis induction in the human CCA cell line(CL-6) suggest that plumbagin could be a promising candidate for CCA chemotherapeutics. However, its relatively low selective cytotoxic effect on CCA cells is a major concern.

Inhibitory effect of plumbagin,a potential anticancer natural compound,on cytochrome P450 2J2 in humans

OBJECTIVE Cytochrome P450(CYP)2J2 is highly expressed in many kinds of human tumors and promotes tumor cell growth via regulating the metabolism of arachidonic acids.The purposes of this study were toidentify the new inhibitor of CYP2J2 from natural compounds and evaluate its potential to inhibit hepatoma carcinoma cells.METHODS Total fifty natural products were screened for the inhibitory potency against the activity of CYP2J2-mediated astemizole O-demethylation via LCMS/MS analysis.Enzyme kinetic and molecular docking studies were also carried out.RESULTS Our data found that plumbagin potently inhibited CYP2J2 with IC50value at 3.42,3.37 and 1.17μmol·L-1in rat liver microsomes,human liver microsomes(HLMs)and recombinant CYP2J2(rC YP2J2),respectively.Further enzyme kinetic studies showed that plumbagin was a mixed-type inhibitor of CYP2J2 in HLMs and r CYP2J2 with Kivalues of 1.88and 0.92μmol·L-1,respectively.Docking data presented that plumbagin interacted with CYP2J2 mainly through GLU222 and ALA223,which were crucial residues for substrates binding.At the same time,plumbagin showed cytotoxicity effects on hepatic carcinoma cell lines,such as HepG 2 and SMMC-7721,with IC50values at 11.55±1.06and(13.15±1.11)μmol·L-1,respectively.CONCLUSION These results indicated that plumbagin was a potent CYP2J2 inhibitor and potential anticancer agent.Further studies are needed to cover the mechanism of its antitumor activity.

Effects of plumbagin on migration and invasion of human hepatoma cell line via JAK2/STAT3 signaling pathway

Objective:To study the effect of plumbagin(PL)on the migration and invasion of human hepatocellular carcinoma(HCC)cells and its possible mechanism.Methods:The cell counting kit(CCK-8)was used to detect the effects of different concentrations of plumbagin on the proliferation of human hepatocellular carcinoma Huh-7 and LM3 cells.The effect of plumbagin on the migration ability of Huh-7 and LM3 cells was detected by scratch test and Transwell migration test,and the effect of on the invasion ability of Huh-7 and LM3 cells was detected by Transwell invasion test.Western Blot was used to detect the expression of E-cadherin,N-cadherin,matrix metalloproteinase-2 and related proteins in JAK2/STAT3 signaling pathway in Huh-7 and LM3 cells.Results:Plumbagin could inhibit the proliferation of Huh-7 and LM3 cells in a time-and concentration-dependent manner.Plumbagin inhibited the migration and invasion of Huh-7 and LM3 cells in a concentration dependent manner,and it can down-regulate the expression of N-cadherin and MMP-2 protein,up-regulate the expression of E-cadherin protein,and inhibit the activation of JAK2/STAT3 signaling pathway.Conclusion:Plumbagin can inhibit the migration and invasion of human hepatocellular carcinoma Huh-7 and LM3 cells,and the molecular mechanism of this process may be related to the inhibition of JAK2/STAT3 signaling pathway activation.

Research Progress and Ideas on the Anti-liver Fibrosis Effect of Ethnic Medicine Plumbagin Based on microRNAs/TLR4/NF-κB and NLRP3 Inflammasome Activation

The core of hepatic fibrosis is the activation of hepatic stellate cells.Through the lipopolysaccharide/TLR4/MyD88/NF-κB signal transduction pathway,the inflammatory response in the liver is directly enhanced,and then returns to promote the activation of hepatic stellate cells.And TLR4/MyD88/NF-κB signaling pathway can directly regulate the activation of NLRP3 inflammasome and is an important pathway for activating hepatic stellate cells.TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway is regulated by upstream microRNAs.These miRNAs can significantly regulate the inflammatory response of the liver and the activation behavior of hepatic stellate cells,affecting the formation of liver fibrosis.Previous studies have found that the active ingredient of Guangxi specialty ethnic medicine,plumbagin,has a definite anti liver fibrosis effect,but its mechanism of action is not clear.This paper provides a review of the research progress on the above issues,and further research ideas have been derived from this,stating that"the anti liver fibrosis effect of plumbagin is achieved by regulating miRNA/TLR4/MyD88/NF-κB inflammatory pathway and activating downstream NLRP3 inflammasome".

Preparation Process of Plumbagin Nanomicelle In-situ Gel

[Objectives]To prepare plumbagin nanomicelle(PLB-N)in-situ gel,and optimize the formulation and process.[Methods]PLB-N was prepared by self-assembly method,and the optimal formulation of PLB-N in-situ gel was determined by orthogonal experiment design and single factor method.[Results]The optimal preparation process for PLB-N was a drug to lipid ratio of 1:3,a Tween 80 content of 5%,an ethanol content of 7.5%of the hydration medium,a magnetic stirring speed of 2200 rpm,a stirring time of 30 min,and an ultrasound time of 10 min.The optimal formulation of PLB-N in-situ gel was 22%of poloxamer 407,6%of poloxamer 188,and 1:1 of PLB-N to water.The encapsulation efficiency of PLB-N prepared with the optimal formula was(95.8%±0.4%),and the average particle size was(75.19±1.14)nm,and the Zeta potential was(-20.73±1.19)mv.[Conclusions]PLB-N in-situ gel had stable and reliable preparation process,uniform content,and broad application prospects.

Research on the Antitumor Effect of Plumbagin by Inhibiting IL-6/STAT3 Pathway in Large Cell Lung Cancer

Background and Objective Lung cancer, which has become the leading cause of tumor mortality in many countries, appears to be one of the most dangerous malignant tumors that

Plumbagin对人高转移大细胞肺癌细胞系抑制作用的研究

目的:研究Plumbagin对人高转移大细胞肺癌L9981细胞系的体外抗肿瘤作用,并初步探讨其机制。方法:不同浓度Plumbagin处理L9981细胞系,采用MTT法观察对肿瘤细胞增殖的影响,确定药物IC50;采用流式细胞术检测对细胞系诱导凋亡的作用;采用Boyden小室侵袭实验检测对体外侵袭力的抑制作用。以IC50Plumbagin处理L9981细胞系,于处理后6、24、48h收获细胞,以实时定量PCR方法检测Bcl-2、Bax、VEGF和CYCD1等基因的mRNA表达变化。结果:MTT法显示,Plumbagin明显抑制L9981细胞系的细胞增殖(F=39.535,P=0.000),IC50为9.0μmol/L;Plum-bagin对L9981细胞系具有体外诱导凋亡作用(F=23.671,P=0.000),且明显抑制其体外侵袭能力。Bodyen小室侵袭实验检测对照组和Plumbagin组平均穿膜细胞数分别为228.17±55.12和9.83±3.87,差异有统计学意义,t=13.598,P=0.000。Plumbagin处理L9981细胞系后不同时间点检测结果显示,Bcl-2、VEGF和CYCD1基因表达均逐渐降低,bax基因表达逐渐增高,组间差异有统计学意义(F=13.520,P=0.000;F=15.778,P=0.000;F=10.163,P=0.000;F=18.635,P=0.000)。结论:Plumbagin对大细胞肺癌L9981细胞系具有明确的抗肿瘤作用。Plumbagin通过多种作用机制发挥其抑癌作用,显示了其成为抗大细胞肺癌药物的前景。

Plumbagin对人类大细胞肺癌NL9980细胞系抑癌作用的研究

目的研究Plumbagin对人类大细胞肺癌NL9980细胞系的抗肿瘤作用并探索其机制。方法不同浓度Plumbagin处理NL9980细胞系，采用MTT法观察其对肿瘤细胞增殖的影响，确定药物IC50，采用流式细胞术检测对细胞系诱导凋亡的作用，采用Boyden小室侵袭实验检测对体外侵袭力的抑制作用；以IC50 Plumbagin处理NL9980细胞系，于处理后6、24及48h收获细胞，以实时定量PCR方法检测bcl-2、bax、VEGF和CYCD1等基因的mRNA表达变化。结果MTT法显示Plumbagin明显抑制NL9980细胞系的细胞增殖，IC50为7．5μmol／L；Plumbagin对NL9980细胞系具有体外诱导凋亡作用，且明显抑制其体外侵袭能力，Bodyen小室侵袭实验检测对照组和Plumbagin组平均穿膜细胞数分别为161．59±47．32和26．58±9．07。Plumbagin处理NL9980细胞系后不同时间点检测结果显示，bcl-2、VEGF和CYCD1基因表达均逐渐减低，bax基因表达逐渐增高，组间差异有统计学意义（均P〈0．05）。结论Plumbagin对大细胞肺癌NL9980细胞系具有明确的抗肿瘤作用。Plumbagin可能通过多种作用机制发挥其抑癌作用，显示了其成为抗大细胞肺癌药物的前景。

Self-assembled metal-organic frameworks nanocrystals synthesis and application for plumbagin drug delivery in acute lung injury therapy

Metal-organic frameworks(MOFs)have recently allured a variety of concern in the fields of nanotechnology.However,exploring their biomedical applications is still a relatively new field.In this work,zeolite imidazole skeleton-8(ZIF-8)was reported for the first time as a drug carrier for the treatment of lung injury.Uniform ZIF-8 nanoparticles encapsulating plumbagin(PLB)are achieved by a facile physical adsorption process.Scanning electron microscopy(SEM),powder X-ray diffraction(PXRD)and UV–vis absorption spectrum were conducted to investigate the physical properties of ZIF-8 and PLB@ZIF-8.In animal model,the collagen fibers deposition produced by severe lung injury is significantly decreased.The secretion of inflammatory factor TGF-βand IL-6 were efficiently dropped by the combination of plumbagin and ZIF-8.At the same time,the expressions of collagen I,α-SMA and TNF-αwere also suppressed.This strategy puts forth a promising blueprint in the application of MOF materials,especially in biomedical fields.

白花丹素通过抑制JAK2/STAT3通路减弱焦亡对抗脓毒症心肌损伤

目的基于网络药理学探讨白花丹素是否通过减轻焦亡来抑制脓毒症心肌损伤的机制。方法通过网络药理学方法获得白花丹素与疾病的关键靶点,进行GO、KEGG分析,通过分子对接验证结合能。将小鼠随机分为4组,8只/组:Sham组、盲肠结扎组(CLP)、白花丹素(PLB,2 mg/kg)+CLP组和PLB(4 mg/kg)+CLP组。采用CLP诱导脓毒症小鼠心脏损伤。超声心动图和HE染色检测心肌功能和形态的变化;检测小鼠血清CK-MB、LDH、MDA和心肌ROS水平,ELISA检测小鼠血清IL-1β和IL-18水平。Western blotting测定心肌STAT3、GSDMD、Caspase-11、JAK2、P-STAT3、P-JAK2、GSDMD-N和HMGB1的蛋白水平。结果从交集的10个基因中筛选出5个核心靶点,分子对接显示,白花丹素与STAT3、p-STAT3和JAK2结合较好。与Sham组相比,CLP组的CO、LVEF、LVFS和SV水平下降(P<0.01)。血清CK-MB、LDH、MDA、心肌炎症因子和ROS水平升高(P<0.01),HE染色结果显示心脏损伤;相关蛋白水平升高(P<0.05)。与CLP组相比,白花丹素处理组的心超功能指标水平升高(P<0.05);血清CK-MB、LDH、MDA、炎症因子和心肌ROS水平降低(P<0.01);相关蛋白水平降低(P<0.05)。结论白花丹素减轻小鼠脓毒症心肌损伤作用,其机制可能与抑制STAT3减轻焦亡有关。

白花丹醌抑制肝癌类干细胞增殖迁移及干性转录因子的表达

目的:探索白花丹醌(Plumbagin, PLB)对肝癌类干细胞增殖迁移及干性转录因子表达的影响。方法:采用多细胞肿瘤球体模式培养富集肝癌类干细胞,设置肝癌细胞组与肝癌类干细胞组,PLB浓度0、5、7.5、10μmol/L组,药物作用时间为24 h,采用MTT法、平板克隆实验、悬浮干细胞成球实验和划痕实验检测细胞增殖、体外成球和迁移能力;qRTPCR和Western blotting检测干性基因和干性蛋白的表达。结果:成功富集肝癌HepG2类干细胞,与肝癌HepG2细胞组比较,肝癌HepG2类干细胞组细胞克隆形成率降低、划痕愈合率和体外成球率升高,差异具有统计学意义(P<0.05);与PLB 0μmol/L组比较,PLB 5、7.5、10μmol/L组,肝癌HepG2类干细胞克隆形成率、体外成球率和划痕愈合率均降低,EpCAM、BMI1、cMYC、Oct4、Nanog干性相关基因及Notch信号通路mRNA的表达水平降低,cMYC蛋白表达水平降低,差异具有统计学意义(P<0.05)。结论:PLB可抑制肝癌HepG2类干细胞增殖、迁移及体外成球能力,从而抑制肝癌细胞干性,其机制可能与下调EpCAM、BMI1、cMYC、Oct4、Nanog干性相关基因和Notch信号通路mRNA的表达水平,以及cMYC蛋白的表达水平有关。

响应面法优化兰雪醌超声辅助提取工艺的研究

目的优化白花丹中兰雪醌超声辅助提取的最佳工艺。方法采用紫外分光光度法分析兰雪醌含量。采用单因素试验考察超声时间、提取温度和料液比对兰雪醌得率的影响,并在单因素试验的基础上使用Box-Behnken响应面法优化得到最佳工艺。结果该模型的调整决定系数(R_(Adj)^(2))为0.8394,回归模型的概率值(P<0.005)显示出较高的显著性。通过Box-Behnke响应面法得到超声提取兰雪醌的最佳工艺参数为超声时间41 min,提取温度42℃,料液比1∶23(g/mL),预测兰雪醌得率为1.823%。在最佳条件下进行了5次验证试验,得到兰雪醌平均得率为1.8941%,与预测值基本吻合。结论利用超声辅助提取方法提取白花丹中兰雪醌的工艺稳定可靠。

RP-HPLC测定民族药材白花丹不同药用部位中白花丹醌的含量

目的：建立白花丹药材中白花丹醌的含量测定方法并考察白花丹不同药用部位中的含量。方法：色谱条件：KromasilCi8柱（4．6mm×200mm，5μm），柱温30℃。流动相甲醇．水（65：35），检测波长213nm，流速1mL·min^-1。结果：白花丹醌在0．0208—0．104μg，峰面积与进样量具有良好的线性关系，回归方程y=-14．29＋9138．9X，r=0．9999，平均回收率为98．7％。白花丹各部位中白花丹醌的含量分别为：根0．394％，茎0．050％，叶0．031％。结论：本法简便、准确、重复性好，可用于控制白花丹药材质量。

中药单体白花丹醌对鲍曼不动杆菌的耐药逆转作用

目的:探索中药单体白花丹醌对临床分离的鲍曼不动杆菌耐药性的逆转作用。方法:取临床分离的鲍曼不动杆菌53株,检测其对临床常用的14种抗菌药物的敏感性。观察中药单体白花丹醌对标准菌株的直接作用。在确定白花丹醌以及羰基氰化氯苯腙(CCCP)的工作浓度以后,观察对比白花丹醌与阳性药CCCP的外排抑制试验结果。结果:临床分离的53株鲍曼不动杆菌对临床常用的14种抗菌药物耐药率较高,其中氨苄西林、头孢唑啉、头孢呋辛、头孢西丁耐药率最高,分别为100%、100%、98.1%、98.1%。其余药物耐药率也均在50%以上。白花丹醌对标准质控菌的直接抗菌作用较弱。而白花丹醌与CCCP均显示了对庆大霉素、诺氟沙星、米诺环素和氯霉素的增敏作用,其外排阳性率分别达11.3%和18.9%,3.8%和7.5%,13.2%和17.0%,28.3%和20.8%,两组之间无统计学差异(P>0.05)。结论:鲍曼不动杆菌临床耐药情况严重,而白花丹醌作为一种中药单体可能具有一定的耐药逆转作用。

紫金莲药材的质量控制方法的研究

目的：建立紫金莲药材的定性鉴别和定量检测方法。方法：采用TLC法，以紫金莲对照药材和白花丹醌对照品鉴别紫金莲药材；以HPLC测定白花丹醌含量。结果：采用C18色谱柱，以甲醇-水（75：25）为流动相，检测波长265nm，供试品色谱中白花丹醌分离良好，白花丹醌进样量在33．6～313．6ng线性关系良好，r=0．9999，平均加样回收率100．3％，RSD1．9％。结论：通过研究制定了紫金莲药材TLC和HPLC质量控制方法。

白花丹醌对人肝星状细胞肿瘤坏死因子-α、血小板衍化生长因子BB表达的影响

目的:研究白花丹醌对瘦素(Leptin)刺激人肝星状细胞(HSC-LX2)肿瘤坏死因子(TNF-α)、血小板衍化生长因子BB(PDGF-BB)表达的影响。方法:体外培养HSC-LX2,瘦素刺激24 h,各药物与细胞共孵育24 h后,采用荧光实时定量PCR检测各组TNF-αmRNA、PDGF-BB mRNA的表达,免疫印迹法测定各组TNF-α和PDGF-BB蛋白表达情况。结果:白花丹醌作用24 h后,与模型组比较,HSC-LX2细胞中TNF-αmRNA和PDGF-BB mRNA的表达水平显著降低。免疫印记结果显示白花丹醌作用24 h后,HSC-LX2PDGF-BB蛋白表达较模型组显著降低(P<0.01)。结论:白花丹醌抑制HSC-LX,TNF-α、PDGF-BB mRNA和抑制PDGF-BB蛋白水平的表达可能是其抗肝纤维化的主要机制之一。

白花丹素减轻免疫球蛋白A肾病大鼠肾损伤的作用及机制

目的探究白花丹素(PLB)对免疫球蛋白A肾病(IgAN)大鼠肾脏损伤的缓解作用及其相关的机制。方法牛血清白蛋白+脂多糖+四氯化碳法建立IgAN大鼠模型,并通过灌胃给予PLB(50,100和200 mg·kg-1)处理。收集尿液检测蛋白尿,取心尖血检测血清肌酸酐(SCr)和尿素氮(BUN)。HE染色观察病理变化,TUNEL染色检测细胞凋亡;专用试剂盒检测肾组织部位氧化应激水平。另设N-乙酰半胱氨酸(NAC)200 mg·kg-1组,Western印迹和ELISA同步检测肾组织IL-18和IL-1β及其前体表达水平,Western印迹法检测肾组织NOD样受体热蛋白结构域3(NLRP3)、接头蛋白凋亡相关点状蛋白(ASC)和胱天蛋白酶1蛋白表达水平。结果与正常对照组比较,模型组肾组织尿蛋白、SCr、BUN浓度,细胞凋亡率和氧化应激水平升高,PLB(50、100和200 mg·kg-1)处理可显著降低肾组织尿蛋白、SCr、BUN含量,降低细胞凋亡及氧化应激水平。同时,NAC 200 mg·kg-1处理可显著降低氧化应激水平,降低IL-18和IL-1β及其前体蛋白表达,降低NLRP3/ASC/胱天蛋白酶1的蛋白表达;与200 mg·kg-1PLB处理有着一致的调控作用。结论 PLB可通过调控ROS抑制NLRP3激活,减轻IgAN大鼠肾脏损伤。