绝经后女性血脂水平与骨密度的相关性研究

目的研究绝经后女性骨密度与血脂水平、体质量指数(BMI)及绝经年限的相关性。方法选择141例绝经后女性作为研究对象,均在骨密度实验室检测骨密度(BMD)水平(主要检测部位为腰椎L_1~4、股骨颈和髋关节,部分病人加做前臂),并根据检测结果(T值为标准)将研究对象分为3组,A组(骨质疏松者,T≤-2.5)、B组(骨量减少者,-2.5 < T < -1.0)和C组(正常骨量病人,T≥-1.0)。同时采集所有研究对象的空腹血,检测其总胆固醇(TC)、低密度脂蛋白(LDL)、三酰甘油(TG) 和高密度脂蛋白(HDL)水平。详细记录病人的身高、体质量、年龄、绝经年龄,计算BMI和绝经年限。结果3组腰椎BMD(LBMD)、股骨颈BMD、全髋关节BMD比较,C组>B组>A组(P < 0.05)。3组HDL、TG、TC水平比较,差异均有统计学意义(P < 0.05~P < 0.01),其中A组HDL水平高于C组(P < 0.05);A组和B组TG水平均低于C组(P < 0.01);C组TC水平低于A组(P < 0.05)。3组LDL水平差异无统计学意义(P < 0.05)。相关性分析显示,年龄和绝经年限与各部位BMD值呈负相关关系(P < 0.05~P < 0.01);身高、体质量及BMI与各部位的BMD呈正相关关系(P < 0.05~P < 0.01)。TG水平与LBMD、股骨颈BMD、全髋关节BMD呈正相关关系(P < 0.01);TC水平与LBMD呈负相关关系(P < 0.05~P < 0.01)。多因素logistic回归分析结果显示,高BMI、高TG者骨质疏松症(OP)发生风险较低,高龄、绝经年限长及高TC者OP发生风险较高。绘制ROC曲线分析TC预测绝经后女性发生OP的价值,计算出AUC为0.636(P < 0.05)。结论绝经后女性不同血脂与不同部位BMD的相关性不同,TC升高与LBMD下降有关,低BMI、高龄、绝经年限长及高TC的绝经后女性更易发生骨质疏松。     

Rapamycin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting IL-1β and IL-18 production

Interleukin (IL)-1β and IL-18 play central and detrimental roles in the development of acute lung injury (ALI), and mammalian target of rapamycin (mTOR) is involved in regulating IL-1β and IL-18 production. However, it is not clear whether the mTOR specific inhibitor rapamycin can attenuate lipopolysaccharide (LPS)-induced ALI by modulating IL-1β and IL-18 production. In this study, we found that rapamycin ameliorated LPS-induced ALI by inhibiting NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated IL-1β and IL-18 secretion. Mechanistically, elevated autophagy and decreased nuclear factor (NF)-κB activation were associated with downregulated IL-1β and IL-18. Moreover, rapamycin reduced leukocyte infiltration in the lung tissue and bronchoalveolar lavage fluid (BALF), and contributed to the alleviation of LPS-induced ALI. Consistently, rapamycin also significantly inhibited IL-1β and IL-18 production by RAW264.7 cells via increased autophagy and decreased NF-κB signaling in vitro. Our results demonstrated that rapamycin protects mice against LPS-induced ALI partly by inhibiting the production and secretion of IL-1β and IL-18. mTOR and rapamycin might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.     

类风湿关节炎患者外周血25羟基维生素D、白介素-6的表达

目的 分析类风湿关节炎(RA)患者血清25羟基维生素D[25(OH)D]、血浆白介素(IL)-6水平及临床意义.方法 选取2019年9月至2021年2月蚌埠医学院第一附属医院治疗的RA患者99例为研究组,按照28个关节疾病活动度(DAS28)评分分为:高度疾病活动期组36例,中度疾病活动期组25例,低度疾病活动期组21...     

Substantia nigra lesion suppresses the antagonistic effects of N-methyl-d-aspartate receptor antagonist (MK-801) on the autotomy in the rat

Rats received right dorsal root ganglionectomy (DRGn) to induce autotomy, and were treated with MK-801 and/or left stantia nigra (SN) lesion after DRGn. The behavior was quantified using an autotomy grading scale. All the rats in the control groups manifested autotomy from 4 to 19 days after DRGn and attained the highest autotomy score. The group treated with MK-801 immediately after DRGn showed suppression of the development of autotomy. The groups receiving left SN lesion with 6-hydroxydopamine immediately, 2, or 4 days after DRGn showed similar patterns of autotomy as the control groups. However, when combined with the administration of MK-801 immediately after DRGn, SN lesion done immediately or 2 days after DRGn suppressed the antagonistic effect of MK-801 (P<0.01). When the SN lesion was delayed by 4 days, the suppression effect disappeared. These data suggest that the action of the NMDA receptor antagonist on the autotomy within 4 days after DRGn depend on the integrity of the dopaminergic system.     

双酚A暴露诱导活性氧水平升高对肝脏脂质代谢的影响

目的探索双酚A(bisphenol A,BPA)对肝脏脂质代谢的影响。方法﹐采用BPA染毒大鼠体内实验,结合人肝细胞系HL-7702体外染毒实验研究双酚A对肝脏脂质代谢的影响。将28只雄性SD大鼠随机分为4组:对照组及BPA亚急性染毒低[1 mg/(kgd)]、中[5 mg/(kg·d)]和高[25 mg/(kg·d)]剂量组,14d后从大鼠体重、肝脏脏器系数,肝脏病理组织切片、血清生化指标等方面评价BPA对肝脏的毒性效应。将人肝细胞系HL-7702,分为对照组及BPA低(0.16 μmol/L)、中(4 μmol/L)和高(100 μmol/L)浓度处理组,染毒24 h后检测细胞内甘油三酯和总胆固醇(totalcholesterol,TC)含量,活性氧簇(reactive oxygen species,ROS)水平,并通过荧光定量PCR检测脂代谢及氧化应激相关基因的转录水平。结果BPA 14 d亚急性染毒后,大鼠体重和肝脏脏器系数无明显变化,但肝脏病理切片发现BPA染毒可损伤肝脏的组织结构。血清生化指标中总胆汁酸在高剂量组显著降低,为(4.75±0.33)μmol/L;肌酐在中﹑高剂量组显著升高,分别为(18.00±0.76)和(18.83±0.75)μmol/L;TC,高密度脂蛋白胆固醇和低密度脂蛋白胆固醇在中,高剂量组均显著降低(P<0.05),分别为(1.44±0.10)、(1.14±0.10)mmol/L,(0.84±0.04)、(0.63±0.07)mmol/L和(0.21±0.04),(0.16±0.05)mmol/L。BPA染毒可使人肝细胞系HL-7702细胞内TC含量显著降低(P<0.05),ROS水平显著增加;PPARα及FABP1转录水平在高浓度处理组中显著升高;SOD1在中,高浓度处理组中均显著降低(P<0.05)。结论BPA可能通过诱导肝脏细胞内产生过量的ROS,导致肝脏损伤和体内脂质代谢紊乱,从而表现出肝脏毒性。     

桑黄酮抑制NLRP3炎症小体活化并缓解感染性休克的作用研究

目的探究桑枝提取物桑黄酮对NLRP3炎症小体活化的影响, 为相关炎性疾病的治疗提供新思路。方法在细胞水平上, 使用Western blotting和ELISA方法, 检测小鼠骨髓来源的巨噬细胞(BMDM)和人THP-1细胞在尼日利亚菌素、单钠尿酸盐和腺嘌呤核苷三磷酸(ATP)3种刺激剂诱导下的半胱氨酸蛋白酶-1(Caspase-1)和白细胞介素(IL)-1β表达水平。在动物实验中, 构建脂多糖(LPS)诱导的感染性休克模型, 将实验小鼠分为安慰剂组、感染性休克组和桑黄酮干预组, 利用ELISA检测小鼠腹腔灌洗液及血清中IL-1β和肿瘤坏死因子-α(TNF-α)水平。结果在BMDM和THP-1细胞中, 桑黄酮可以抑制尼日利亚菌素、单钠尿酸盐和ATP这3种炎症小体激动剂诱导的Caspase-1和IL-1β的加工和成熟(P < 0.01), 而对非炎症小体相关的细胞因子TNF-α的分泌无影响(P>0.05)。在动物实验中, 发现桑黄酮可以缓解LPS诱导的小鼠感染性休克(P < 0.01), 明显抑制LPS诱导的小鼠血清及腹腔液中IL-1β的表达(P < 0.01), 延长LPS造模后小鼠的存活时间(P < 0.01)。结论桑黄酮作为一种中草药活性成分提取物, 可以在体外和体内抑制NLRP3炎症小体的活化, 为NLRP3相关疾病的治疗提供了实验依据。     

Elevated RAP1A expression correlates with the severity of acute GVHD after umbilical cord blood transplantation

BackgroundAcute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation. Ras-related protein 1A (RAP1A) has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in aGVHD remains unclear.ObjectiveTo study the role of RAP1A in the pathogenesis of aGVHD.Material and methodsStudy participants included six patients with grade 2–4 aGVHD, 13 patients with grade 1 aGVHD, 11 patients without aGVHD, and 12 healthy people. The expression level of RAP1A in whole cells was detected by western blot and qRT-PCR. The proportions of CD4⁺CD25⁺FoxP3⁺ Treg cells (T regulatory cells) and the expression of RAP1A in Treg cells in peripheral blood mononuclear cells (PBMCs) were detected by flow cytometry and the levels of related cytokines in the serum was detected by cytometric bead array.ResultsWe found the level of RAP1A was higher in patients than in healthy individuals. A negative correlation was noted between RAP1A and the number of Treg cells. In addition, the level of IL-10 in patients with grade 2–4 aGVHD was significantly lower than that in healthy donors, however, the level of TNF-ɑ in patients with grade 2–4 aGVHD was higher. Furthermore, we found a negative correlation between levels of IL-10 and RAP1A, and a positive correlation between TNF-ɑ and RAP1A.ConclusionThe expression of RAP1A in patients with aGVHD was significantly increased, and shows potential as a target for the prevention and treatment of aGVHD.