IL-4/IL-4R对肝细胞癌生物学行为的影响及潜在的作用机制北大核心CSCD

目的检测白细胞介素-4/白细胞介素-4受体(Interleukin-4/Interleukin-4 receptor,IL-4/IL-4R)对肝细胞癌(hepatocellular carcinoma,HCC)生物学行为的影响及潜在的作用机制。方法体外培养Huh7细胞,并进行转染,沉默细胞中IL-4R基因的表达。CCK8法检测细胞增殖。流式细胞术检测细胞凋亡和细胞周期。Western blot法探索可能的作用机制。结果 IL-4促进Huh7细胞的增殖(P=0.01),沉默IL-4R可抑制Huh7细胞的增殖(P=0.00033),且细胞早期凋亡增加(P=0.014),凋亡蛋白Bax(P=0.016)和Caspase-3(P=0.029)表达增加,抗凋亡蛋白Bcl-2(P=0.003)表达减少。沉默IL-4R并不影响细胞晚期凋亡(P=0.108)及细胞周期(G_0/G_1期:P=0.677、S期:P=0.139、G_2/M期:P=0.855)变化。IL-4促进JAK1(P=0.01)和STAT6(P=0.005)的磷酸化。沉默IL-4R后细胞内JAK1(P=0.016)和STAT6(P=0.019)的磷酸化水平均降低。结论 IL-4/IL-4R可以激活HCC内JAK1/STAT6信号通路、促进HCC的增殖。此外,还通过调节凋亡蛋白和抗凋亡蛋白的表达,最终抑制细胞凋亡。     

脂多糖干预对大鼠周围神经损伤后瓦勒变性的影响

目的 探讨脂多糖对于大鼠坐骨神经损伤瓦勒变性早期髓鞘碎片清除的影响。 方法 将50只Wistar大鼠随机分成假手术组（10只）,模型组（20只）和脂多糖LPS组（20只）,LPS组及模型组横断大鼠右侧坐骨神经后,行神经外膜端端吻合;假手术组仅游离出坐骨神经,然后关闭切口。LPS组大鼠在神经断端显微注射LPS （2 g/ L） 1 μL,模型组及假手术组大鼠注射同等体积生理盐水。于术后1.5、24 h和7 d 取术侧坐骨神经。实时定量PCR（qRT-PCR）检测坐骨神经中白介素1β（IL-1β）mRNA、单核细胞趋化蛋白-1 （MCP-1） mRNA水平;免疫荧光法检测坐骨神经中CD68⁺巨噬细胞的表达;HE染色观察坐骨神经的病理变化;油红O染色观察坐骨神经脱髓鞘程度;LFB染色观察坐骨神经髓鞘变化;坐骨神经功能指数（SFI）评价大鼠运动功能的恢复情况。结果 实时定量PCR显示,与假手术组相比,术后1.5 h模型组IL-1β mRNA和MCP-1 mRNA的表达均明显升高（P < 0.001,P < 0.001）,与模型组相比,术后1.5 h LPS组IL-1β mRNA和MCP-1mRNA的表达明显升高（P < 0.001,P < 0.001）。术后24 h模型组IL-1β mRNA和MCP-1m RNA的表达均明显升高（P < 0.001,P < 0.001）,与模型组相比,术后24 h LPS组IL-1β mRNA和MCP-1 mRNA的表达明显升高（P < 0.01,P < 0.01）。免疫荧光可见,与模型组相比,术后7 d LPS组中CD68⁺细胞表达显著上调（P < 0.05）。术后7 d坐骨神经HE染色可见,LPS组坐骨神经断端较多炎性细胞浸润,许旺细胞增殖活跃,模型组神经断端炎性细胞和许旺细胞较少。术后7 d坐骨神经ORO染色可见,与模型组相比,LPS组断端远侧脱髓鞘程度较高。术后7 d坐骨神经LFB染色可见,模型组和LPS组坐骨神经断端均出现脱髓鞘反应,但与模型组相比,LPS组神经断端残余髓鞘碎片明显减少（P < 0.05）。SFI显示,与模型组相比,LPS组大鼠在术后10、20、30、40和50 d分别不同程度升高,术后20 d明显增高,差异有显著性（ P < 0.05）。结论 脂多糖通过激活固有免疫系统加快大鼠坐骨周围神经损伤后瓦勒变性早期髓鞘碎片的清除。     

TOLL样受体4拮抗剂干预周围神经损伤后的瓦勒变性

BACKGROUND: The mechanism underlying Wallerian degeneration following peripheral nerve injury is complex. Immune regulation on Wallerian degeneration is beneficial for early repair of perpheral nerve injury. OBJECTIVE: To investigate the effects of Toll-like receptor 4 (TLR4) antagonist on Wallerian degeneration and axonal regeneration after early peripheral nerve injury in rats. METHODS: Fifty male Wistar rats were recruited and randomly divided into treatment group (n=20), model group (n=20) and sham group (n=10). The right sciatic nerves of rats in treatment and model groups were cut and sutured end-to-end, while the sciatic nerves of rats in sham group were only exposed. In the treatment group rats were intravenously injected with 0.15 mg/kg TAK-242 via tail vein 1 hour preoperatively and 7 days postoperatively, and the rats in the other two groups were given intravenous injection of the same volume of normal saline. The sciatic nerves were removed at 24 hours, 3, 4 and 7 days after surgery. RESULTS AND CONCLUSION: Real-time PCR indicated that the mRNA expressions of interleukin-1β and monocyte chemoattractant-1 were significantly increased in the model group compared with the sham group at 24 hours after surgery (both P < 0.001), while the expressions were significantly decreased after TAK-242 injection (both P < 0.001). Immunofluorescence showed that compared with the model group, down-regulated expression of CD68+ and iba1+ cells appeared in the treatment group at 3 days after surgery (P < 0.01, P < 0.05). Luxol fast blue staining revealed that demyelination at the sciatic nerve stump appeared in both model and treatment groups at postoperative 7 days, but myelin debris clearance in the treatment group was significantly reduced compared with the model group (P < 0.05). Hematoxylin-eosin staining showed that a lot of inflammatory cells, Schwann cells and regenerated nerve fibers at the sciatic nerve stump were found in the model group, while there were few inflammatory cells, Schwann cells and regenerated nerve fibers in the treatment group at 7 days after surgery. Immunohistochemistry found that the expression of growth-associated protein-43 in the treatment group was significantly lower than that in the model group at 4 days postoperatively (P < 0.05). Besides, compared with the model group, a significantly decreased sciatic functional index was found in the treatment group at 20, 30 and 40 days after surgery (P < 0.05). These results show that TLR4 antagonists delay early nerve regeneration in rats after sciatic nerve injury probably by inhibiting the TLR4 signaling pathway. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

放射性心脏损伤的病理基础及生物学机制

 心血管疾病与肿瘤是世界范围内发病率及死亡率最高的两种疾病。目前,放射治疗是恶性肿瘤治疗的重要手段之一。对于胸部肿瘤进行放射治疗时,心脏不可避免的接受不同程度剂量射线,导致放射性心脏损伤。本文就放射性心脏损伤的病理基础及生物学机制作了详细的阐述,以探索放射性心脏损伤的潜在治疗靶点。