坐骨神经缺损后神经组织再生早期信号调控研究

目的:采用基因芯片技术结合信号传递调控网络(Signal-Flow)分析技术,探讨坐骨神经缺损近端神经组织早期分子信号调控机理。方法:SD大鼠坐骨神经缺损0h、0.5h、1h、3h、6h和9h后,取0.5cm近端神经组织进行mRNA芯片检测,进行差异基因的筛选和信号传递调控网络分析,并采用qRT-PCR对相关基因行表达趋势验证。结果:共筛选差异显著性基因2850个,抗凋亡相关因子和紧密连接蛋白等构成信号传递调控网络的核心部分。Birc2、Birc3和Tnfrsf1a早期上调抑制凋亡相关基因,紧密连接蛋白cldn14促进与其家族成员的结合。结论:抗凋亡因子和紧密连接蛋白可能是坐骨神经缺损后神经组织再生的内在早期调控分子,推测与神经组织损伤后内在的再生能力调控机制相关。     

Natural products: potential treatments for cisplatin-induced nephrotoxicity

Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%–35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.     

金丝桃苷保护大鼠脑缺血再灌注损伤的机制研究

目的 探究金丝桃苷（hyperoside，Hyp）对脑缺血再灌注大鼠脑组织的保护作用及相关机制。方法 采用线栓法建立大脑中动脉闭塞/再灌注（middle cerebral artery occlusion/reperfusion，MCAO/R）大鼠模型，分成假手术组、模型组、Hyp低、中、高剂量组（30，60，120 mg·kg^-1）。持续给药14 d后，采用Zea Longa法对大鼠进行神经功能评分，并测定脑含水量。TTC染色法测定大鼠脑梗死体积，ELISA检测炎症相关因子，HE染色观察大脑海马CA1区神经元病理形态，TUNEL染色观察大鼠脑组织细胞凋亡程度，Western blotting检测TLR4和COX-2以及凋亡相关蛋白的表达。结果 Hyp干预能够显著改善MCAO/R大鼠Zea Longa评分（P<0.05），减少脑含水量和脑梗死体积，显著降低炎症因子（TNF-α、IL-1β、IL-6、ICAM-1以及VCAM-1）的表达（P<0.05或P<0.01），并且有效改善海马CA1区神经元的病理学改变和凋亡情况，显著抑制TLR4、COX-2、NF-kB、caspase-3、caspase-9以及Bax蛋白的表达（P<0.05或P<0.01），上调Bcl-2蛋白的表达（P<0.05）。结论 Hyp对脑缺血再灌注损伤的保护作用与抗炎、抗凋亡以及抑制TLR4/COX-2信号通路有关。     

槲皮素防治急性肝损伤作用机制的研究进展

急性肝损伤是一种严重的疾病，其发病机制和影响因素多种多样，其中药物治疗是目前急性肝损伤的主要治疗方法。槲皮素为黄酮醇类化合物，可通过抗炎、抗氧化应激反应、抗肝纤维化、抗细胞凋亡、增强细胞自噬、抑制转运体NTCP的表达降低胆汁酸重吸收、调节肝脏脂质代谢，多途径减轻肝损伤，发挥肝保护作用。总结了槲皮素防治急性肝损伤的作用机制，为急性肝损伤治疗提供参考。