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1.
目的探讨胱天蛋白酶募集域蛋白9(CARD9)在大鼠急性胰腺炎相关性肺损伤(APALI)中的作用及机制。方法30只雄性Sprague Dawley大鼠采用随机数字表法分成对照组(6只)、APALI组(12只)、腺病毒干扰组(12只)。通过胰管注射牛磺胆酸钠建立重症急性胰腺炎(SAP)大鼠模型,造模后3、6 h处死动物。苏木精-伊红(HE)染色评估胰腺组织及肺组织的病理改变。采用时聚合酶链反应(RT-PCR)检测肺组织中CARD9、p65核因子-κB(p65NF-κB)、p38丝裂原活化蛋白激酶(p38MAPK)的转录水平。采用酶联免疫吸附法(ELISA)检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平及肺组织中髓过氧化物酶(MPO)水平。蛋白质印迹法(Western blot)检测肺组织中CARD9、p-p65NF-κB、p-p38MAPK蛋白表达水平。组间数据比较采用单因素方差分析,最小显著性差异法(LSD)法或Tamhane’s T2法进行两两比较。结果APALI组3、6 h肺组织中CARD9 mRNA水平均高于Control组[3 h(5.572±0.722)、6 h(12.588±2.008)比(0.991±0.066),F=134.738,t=15.475、14.139,P值均<0.05],差异均有统计学意义;腺病毒干扰组3、6 h CARD9 mRNA水平均低于APALI组相同时间点[3 h(3.079±0.348)比(5.572±0.722)、6 h(7.945±1.538)比(12.588±2.008),F=55.899,t3 h=7.618、t6 h=4.497,P值均<0.05],差异均有统计学意义。造模后3、6 h,APALI组肺组织中NF-κB mRNA、p38MAPK mRNA水平均高于对照组[NF-κB 3 h(6.746±0.894)、6 h(15.116±1.939)比(0.973±0.076),p38MAPK 3 h(4.422±0.369)、6 h(6.405±0.590)比(0.973±0.536),tNF-κB=15.766、17.849,tp38MAPK=22.686、22.469,P值均<0.05],差异均有统计学意义;造模后3、6 h,腺病毒干扰组的NF-κB mRNA、p38MAPK mRNA水平分别低于APALI组同时间点[NF-κB 3 h(4.002±0.543)比(6.746±0.894)、6 h(8.771±0.805)比(15.116±1.939),p38MAPK 3 h(2.705±0.232)比(4.422±0.369)、6 h(5.372±0.401)比(6.405±0.590),tNF-κB=6.430、7.401,tp38MAPK=9.969、3.351,P值均<0.05],差异均有统计学意义。结论APALI大鼠肺组织中存在CARD9相关的NF-κB、p38MAPK信号通路,可通过抑制CARD9表达、减轻炎性反应对APALI发挥保护作用。  相似文献   
2.
目的探讨神经妥乐平对帕金森病(PD)大鼠的神经保护作用及其相关机制。方法 SD大鼠分为对照组、PD组(PD造模)、神经妥乐平低剂量组(PD造模+腹腔注射0.6 Nu·kg-1神经妥乐平溶液)、神经妥乐平高剂量组(PD造模+腹腔注射1.2 Nu·kg-1神经妥乐平溶液)和通路抑制组(PD造模+腹腔注射1.2 Nu·kg-1神经妥乐平溶液及2 mg·k-1 Nrf2通路抑制剂Brusatol)。转棒试验及爬杆试验测试大鼠的行为功能,记录跌落潜伏期、爬下时间;苏木精-伊红染色观察脑组织病理变化;试剂盒检测脑组织中过氧化氢酶(CAT)活性、丙二醛(MDA)含量及白细胞介素(IL)-6、IL-1β水平;蛋白印迹检测脑组织中核因子E2相关因子2 (Nrf2)、血红素加氧酶-1 (HO-1)和醌氧化还原酶1 (NQO1)蛋白表达。结果与对照组相比,PD组大鼠跌落潜伏期显著缩短(P<0.05),脑组织中CAT活性、Nrf2、HO-1、NQO1蛋白表达水平显著降低(P<0.05),爬下时间显著延长(P<0.05),脑组织中MDA含量、IL-6、IL-1 β水平显著升高(P<0.05),脑组织出现病理改变;与PD组相比,神经妥乐平低、高剂量组大鼠跌落潜伏期显著延长(P<0.05),脑组织中CAT活性、Nrf2、HO-1、NQO1蛋白表达水平显著升高(P<0.05),爬下时间显著缩短(P<0.05),脑组织中MDA含量、IL-6、IL-1 β水平显著降低(P<0.05),脑组织病变减轻;与神经妥乐平高剂量组相比,通路抑制组大鼠跌落潜伏期显著缩短(P<0.05),脑组织中CAT活性、Nrf2、HO-1、NQO1蛋白表达水平显著降低(P <0.05),爬下时间显著延长(P <0.05),脑组织中MDA含量、IL-6、IL-1 β水平显著升高(P<0.05),脑组织病变程度加重。结论神经妥乐平可改善脑组织氧化应激、炎症损伤状态,提高PD大鼠行为功能,其机制可能与激活Nrf2/HO-1/NQO1通路有关。  相似文献   
3.
目的:本实验建立一种有效的河豚毒素毒性检测细胞模型,为河豚毒素解毒药物高通量筛选奠定基础。方法: 用不同浓度膜电位荧光探针DiBAC4(3)在全黑底透96 孔细胞培养板中孵育SH-SY5Y 人神经母细胞瘤细胞,利用 不同浓度藜芦定使细胞去极化,利用荧光酶标仪测定不同浓度河豚毒素对细胞膜电位的影响。结果:以DiBAC(4 3) 1000 nmol/L、藜芦定200 μmol/L、河豚毒性100 μmol/L 作用于SH-SY5Y 细胞,观察到河豚毒素使该细胞膜电位 变化最显著。结论:通过测量毒素诱导的膜电位变化可以初步预测和量化河豚毒素的毒性,可用于筛选解毒剂。 该方法操作简便,并且可以实现高通量自动化筛选。  相似文献   
4.
《Drug discovery today》2022,27(1):82-101
WNT/β-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/β-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/β-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/β-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/β-catenin inhibitors to the clinic for cancer therapy.  相似文献   
5.
ObjectiveWe present the application of quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid confirmation of trisomy 13 of maternal origin in a pregnancy with fetal holoprosencephaly (HPE), cyclopia, polydactyly, omphalocele and cell culture failure.Case reportA 21-year-old, gravida 2, para 0, woman was referred for termination of the pregnancy at 17 weeks of gestation because of the abnormal ultrasound finding of alobar HPE. The pregnancy was subsequently terminated, and a 118-g malformed male fetus was delivered with cyclopia, bilateral postaxial polydactyly of the hands and ruptured omphalocele. Postmortem cell culture of the placental tissue and umbilical cord was not successful. The parental karyotypes were normal. QF-PCR analysis using the polymorphic DNA markers of D13S1810, D13S790 and D13S251 on the DNA extracted from placenta, umbilical cord and parental bloods showed trisomy 13 of maternal origin.ConclusionPerinatal diagnosis of concomitant HPE, polydactyly and omphalocele should raise a suspicion of fetal trisomy 13. QF-PCR analysis is useful for rapid confirmation of trisomy 13 and the parental origin especially under the circumstance of cell culture failure, and the information acquired is very useful for genetic counseling of the parents.  相似文献   
6.
7.
BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage(APD)attenuates intestinal mucosal injury in rats with severe acute pancreatitis(SAP),and improves administration of enteral nutrition in patients with acute pancreatitis(AP).However,the underlying mechanisms of the beneficial effects of APD remain poorly understood.AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats,and its potential mechanisms.METHODS SAP was induced in male adult Sprague-Dawley rats by 5%sodium taurocholate.Mild AP was induced by intraperitoneal injections of cerulein(20μg/kg body weight,six consecutive injections).Following SAP induction,a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD.Morphological changes,serum inflammatory mediators,serum and ascites high mobility group box protein 1(HMGB1),intestinal barrier function indices,apoptosis and associated proteins,and toll-like receptor 4(TLR4)signaling molecules in intestinal tissue were assessed.RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP,as demonstrated by decreased pathological scores,serum levels of D-lactate,diamine oxidase and endotoxin.APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells,and normalized the expression of apoptosis-associated proteins in intestinal tissues.APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1,thus exerting protective effects against SAP-associated intestinal injury.CONCLUSION APD improved intestinal barrier function,intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats.The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.  相似文献   
8.
Objective: To study the effect and mechanism of Huayu Wan (化瘀丸, HYW) in combination of chemotherapy of tumor treatment. Methods: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the efficacy of doxorubicin was studied. Results: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). Conclusions: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the efficacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.  相似文献   
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10.
近几年,"劳务派遣"成了医疗机构终末消毒、保洁、垃圾回收等工作新的用工形式。由于多数用工单位和用人单位不清楚对劳务派遣人员职业健康管理中各自应承担的责任和义务,以至于劳务派遣工在劳动过程中应享有的劳动保护权益未获得切实保障。本文就某医疗机构核医学工作场所劳务派遣保洁人员的职业健康管理监督案例进行讨论。  相似文献   
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