NF-κB对尿白蛋白诱导肾小管上皮细胞骨桥蛋白转录的影响

目的研究NF-κB对尿白蛋白诱导肾小管上皮细胞骨桥蛋白转录的影响。方法去脂的小牛血清白蛋白(BSA)20mg/ml分别加入到体外培养的肾小管上皮细胞和加入NF-κB抑制剂(PDTC)共同培养半小时的肾小管上皮细胞内,EMSA、RT-PCR检测不同时限NF-κB活性、骨桥蛋白mRNA表达情况。结果去脂的小牛血清白蛋白可刺激肾小管上皮细胞内NF-κB活性增加,骨桥蛋白mRNA表达上调,而提前加入NF-κB抑制剂(PDTC)共同培养半小时的肾小管上皮细胞内NF-κB活性、骨桥蛋白mRNA表达明显下降。结论尿白蛋白诱导小管上皮细胞损伤的机制与诱导肾小管上皮细胞内NF-κB活性、骨桥蛋白mRNA增加有关,而且骨桥蛋白转录由NF-κB调控。     

Saccades and multisaccadic gaze shifts are gated by different pontine omnipause neurons in head-fixed cats

 Pontine omnipause neurons (OPNs) have so far been considered as forming a homogeneous group of neurons whose tonic firing stops during the duration of saccades, when the head is immobilized. In cats, they pause for the total duration of gaze shifts, when the head is free to move. In the present study, carried out on alert cats with fixed heads, we present observations made during self-initiated saccades and during tracking of a moving target which show that the OPN population is not homogeneous. Of the 76 OPNs we identified, 39 were found to have characteristics similar to those of previously described neurons, ”saccade” (S-) OPNs: (1) the durations of their pauses were significantly correlated with the durations of saccades; (2) the discharge ceased shortly before saccade onset and resumed before saccade end; (3) visual responses to target motion were excitatory; and (4) during tracking, S-OPNs interrupted the discharge for the duration of saccades and resumed firing during perisaccadic ”drifts”. However, the characteristics of 37 neurons (”complex” (C-) OPNs) were different: (1) the pause duration was not correlated with the duration of self-initiated saccades; (2) time lead of pause onsets relative to saccades was, on average, longer than in the group of S-OPNs, and firing resumed after the saccade end; (3) visual target motion suppressed tonic discharges; and (4) during tracking, firing was interrupted for the total duration of gaze shifts, including not only saccades but also perisaccadic ”drifts”. We conclude that cat OPNs can be subdivided into two main groups. The first comprises neurons whose firing patterns are compatible with gating individual saccades (”saccade” OPNs). The second group consists of ”complex” OPNs whose firing characteristics are appropriate to gate total gaze displacements rather than individual saccades. The function of these neurons may be to disinhibit pontobulbar circuits participating in the generation of saccade sequences and associated perisaccadic drifts. Received: 20 January 1998 / Accepted: 22 October 1998     

泽泻有效部位对肾草酸钙结石模型大鼠肾组织骨桥蛋白表达的影响

目的研究泽泻有效部位对大鼠肾草酸钙结石形成和肾组织骨桥蛋白(OPN)表达的影响,探讨泽泻抑制尿结石形成的机制。方法采用现代植化和生物活性导向分离的方法分离、提取泽泻的有效部位。将30只大鼠随机分成3组对照组、模型组、泽泻组。以乙二醇和1α-羟基维生素D3ig制备大鼠肾草酸钙结石模型。检测各组大鼠血及尿生化、肾Ca2 水平、24h尿草酸分泌量和肾组织病理学改变,并采用免疫印迹(Western blotting)和半定量逆转录聚合酶链反应(RT-PCR)分别观察各组大鼠肾组织OPN蛋白及其mRNA的表达水平。结果ig泽泻有效部位(主要以四环三萜类化合物为主)大鼠的血清肌酐(SCr)、尿素氮(BUN)、肾Ca2 水平、24h尿Ca2 分泌量、肾组织草酸钙晶体的分布、OPN蛋白及其mRNA的表达水平均显著低于模型组(P<0.01)。结论泽泻有效部位能抑制大鼠肾组织OPN的表达,减少肾组织草酸钙结晶的沉积,从而能有效抑制大鼠肾草酸钙结石的形成。     

创伤后感染致多器官功能障碍综合征患者血清β-hBD-2、OPN、pro-ADM和NPt水平的变化

目的：探讨多器官功能障碍综合征（multipleorgandysfunctionsyndrome,MODS）患者的炎症感染病理过程中炎性介质水平的变化。方法：血清人类B防御素-2（humanB．defensin-2,β—hBD-2）、骨桥蛋白（osteopontin,OPN）和新蝶呤（neoptefin,NPt）采用酶联免疫分析法（ELISA）测定,肾上腺髓质素前体（pro-adrenomeduUin,pro—ADM）检测采用化学免疫发光法。结果：四项血清标志物测定结果分别显示,对照组和确诊时组B-hBD-2、OPN、pro-ADM、NPt四种血清炎症介质标志水平均显著高于正常人组（P〈0．05,P〈0．01）,出院前组β-hBD-2、OPN水平显著高于正常人组,另两项指标均与正常人组比较无显著性差异（P均〉0．05）;同时确诊时组与对照组比较β—hBD-2、OPN、pro-ADM三项指标水平也显著升高（P〈0．05,P〈0．01）,NPt水平患者组呈略高,但无统计学意义（P〉0．05）;出院前组β-hBD-2、OPN、pro-ADM、NPt四种血清炎症介质标志水平均显著低于确诊时组（P〈0．05,P〈0．01）。结论：MODS患者的炎症感染病理过程中炎性介质水平显著升高,其测定对于临床抗感染治疗提供重要价值。     

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.     

Osteopontin-deficient progenitor cells display enhanced differentiation to adipocytes

ObjectiveOsteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation.MethodsOPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1^−/− female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1^−/− mice (n = 15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR.ResultsWe show that Spp1^−/− maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1^−/− mice. Strikingly, APC from Spp1^−/− were diminished but differentiated more efficiently to adipocytes than those from control mice.ConclusionsAPC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance.     

乌苯美司联合XEC化疗方案治疗三阴性乳腺癌的临床研究

目的探讨乌苯美司联合XEC化疗方案治疗三阴性乳腺癌患者的临床疗效及其对外周血T淋巴细胞亚群及血清骨桥蛋白(OPN)水平变化的影响。方法选取河南科技大学第一附属医院2015年6月—2017年1月收治的三阴性乳腺癌患者83例,随机分成对照组(41例)和治疗组(42例)。对照组患者给予XEC化疗方案治疗,第1天静脉滴注注射用环磷酰胺500 mg/m~2,同时静脉滴注注射用盐酸表柔比星100 mg/m~2,第1~14天口服卡培他滨片1 g/m~2,疗程为21 d。治疗组在对照组的基础上口服乌苯美司片,30 mg/次,1次/d,疗程为21 d。两组均持续治疗4个疗程。观察两组患者临床疗效,比较治疗前后两组患者SF-36评分、外周血T淋巴细胞亚群表达水平和OPN水平。结果治疗后,对照组和治疗组临床总有效率分别为75.61%、95.24%,两组比较差异具有统计学意义(P0.05)。治疗后,两组躯体疼痛、躯体功能、睡眠质量、生命活力、生理职能、心理健康等生活质量评分均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组生活质量评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)水平均显著升高,CD~(8+)水平显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组T淋巴细胞亚群水平显著优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清OPN水平显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组血清OPN水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论乌苯美司联合XEC化疗方案治疗三阴性乳腺癌患者效果显著,可有效改善患者外周血T淋巴细胞亚群和血清OPN水平,且安全性较高,具有一定的临床推广应用价值。     

Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice

Osteopontin (OPN) is a chemotactic factor which can be cleaved to the pro-inflammatory form by matrix metalloproteinases (MMPs). To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL). OPN-KO mice showed significant reduction in liver injury (plasma ALT and necrosis) and neutrophil recruitment compared with WT animals at 24 h but not 72 h after BDL. In WT mice, a 4-fold increase in hepatic MMP-3 mRNA and elevated MMP activities and cleaved OPN levels were observed in bile. WT mice subjected to BDL in the presence of the MMP inhibitor BB-94 showed reduced liver injury, less neutrophil extravasation and diminished levels of cleaved OPN in bile. Thus, during obstructive cholestasis, OPN released from biliary epithelial cells could be cleaved by MMPs in bile. When the biliary system leaks, cleaved OPN enters the parenchyma and attracts neutrophils. In the absence of OPN, other chemoattractants, e.g. chemokines, mediate a delayed inflammatory response and injury. Taken together, our data suggest that OPN is the pro-inflammatory mediator that initiates the early neutrophil-mediated injury phase during obstructive cholestasis in mice.