Objective To explore the effect of the Trim44 gene in the nervous system, Trim44 conditional knockout rats were used to analyze behavioral abnormalities and pathological changes in the brain. Methods TRIM44 expression in brain tissue was detected by Western blot and immunohistochemistry. Neuronal apoptosis was determined by TUNEL staining. Behavioral changes of knockout rats were assessed by Morris Y, Morris water, and food maze tests. Abnormal expression of apoptosis-related proteins was detected by Western blot. Results TRIM44 was highly expressed in brain tissues of adult rats. The knockout efficiency of Trim44 in brain tissues was 67%. Trim44 knockout decreased learning and memory abilities, increased neuronal apoptosis, and expression of active caspase 3 and 9 proteins in aged rats. Conclusions Trim44 knockout promotes neuronal apoptosis and impairs learning and memory abilities in rats. These result suggest that TRIM44 plays an important role in the nervous system, and the Trim44 knockout rat model can be used for further mechanism exploration.

目的 研究注射用丹参多酚酸(salvianolic acids for injection,SAFI)对氧糖剥夺后恢复(oxygen and glucose deprivation reperfusion,OGD/R)损伤PC12细胞的保护作用及机制.方法 采用网络药理学方法预测SAFI抗脑缺血再灌注损伤的作用靶点.建立OGD/R损伤PC12细胞模型,采用噻唑蓝(MTT)比色法和检测乳酸脱氢酶(LDH)的释放考察SAFI对PC12细胞活力的影响,吖啶橙/溴化乙锭(acridine orange/ethidium bromide,AO/EB)染色检测细胞凋亡,蛋白质印迹法(Western blot)检测B淋巴细胞瘤-2关联X蛋白(Bax)和B淋巴细胞瘤-2(Bcl-2)凋亡蛋白水平,进一步通过免疫荧光法研究SAFI保护OGD/R损伤PC12细胞的作用通路.结果 OGD/R损伤PC12细胞,导致细胞存活率明显降低,1和10 mg·mL-1的SAFI可以显著提高OGD/R后PC12细胞存活率,降低LDH释放.并且SAFI能够显著增加OGD/R损伤后抗凋亡蛋白Bcl-2的表达,抑制促凋亡蛋白Bax过表达.进一步研究表明,SAFI可以显著上调蛋白激酶B(protein kinase B,Akt)和信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)的磷酸化水平.结论 SAFI 能够抑制 OGD/R 对 PC12 细胞的损伤,是通过促进Bax和Bcl-2平衡的恢复,激活磷脂酰肌醇激酶(PI3K)/Akt和蛋白酪氨酸激酶2(janus kinase 2,JAK2)/STAT3信号通路实现的.

目的 本文利用瘦素受体(LEPR)敲除大鼠,分析瘦素受体基因敲除后大鼠脑中小胶质细胞形态与功能的改变,探究瘦素受体在小胶质细胞中的功能作用.方法 采用RT-PCR,蛋白印迹法,免疫组化法和免疫荧光法,观察大鼠瘦素受体敲除后体内外小胶质细胞活化状态.结果 瘦素受体在小胶质细胞表达,基因敲除可以完全剔除小胶质细胞中LEPR蛋白;LEPR敲除增强大鼠LPS对刺激的炎症反应,存活率降低了75％;LEPR敲除大鼠脑中的活化的小胶质细胞比例明显增加;LEPR敲除的原代小胶质细胞不仅分泌更多炎性因子也增强了吞噬能力;Western blot发现PI3K/AKT在瘦素受体敲除大鼠脑组织蛋白中磷酸化明显增强.结论 瘦素受体敲除后,大鼠小胶质细胞向促炎促吞噬的方向发展,揭示了LEPR/Leptin可能通过小胶质细胞调节神经炎症.

阿尔茨海默病(Alzheimer disease,AD)是一种以痴呆为主要症状的慢性进行性神经退行性疾病,主要神经病理学特征包括老年斑、神经原纤维缠结、神经炎症和神经元丢失.AD中的β-淀粉样蛋白沉积和错误折叠的Tau蛋白诱导小胶质细胞的激活,引起细胞因子、趋化因子的分泌,共同形成神经炎症反应影响AD的发展.本文总结了小胶质细胞激活和趋化因子释放在AD神经炎症中发挥的作用,为AD的治疗提供新的思路.

目的 了解临床分离株中耐碳青霉烯肺炎克雷伯菌(CRKP)的氟喹诺酮类耐药基因及16SrRNA甲基化酶基因存在情况和药敏特点.方法 收集临床标本中分离的6株CRKP,采用VITEK 2 compact全自动微生物鉴定和药敏系统鉴定细菌及药敏试验,采用聚合酶链反应(PCR)扩增氟喹诺酮类耐药基因和16SrRNA甲基化酶基因.结果 6株CRKP临床分离株呈现多药耐药特点,对环丙沙星和左氧氟沙星的耐药率分别是83.3％和83.3％,对庆大霉素、阿米卡星和妥布霉素的耐药率分别是66.7％,50％ 和66.7％.检出喹诺酮类耐药相关基因qnrB,qnrS和qnrD,基因阳性率分别为50％,50％和33.3％,未检出qnrA,qnrC和qepA基因.检出16SrRNA甲基化酶耐药相关基因armA,基因阳性率为50％,未检出rmtA,rmtB,rmtC和npmA基因.结论 6株CRKP对喹诺酮类和氨基糖类抗生素耐药严重,其耐药性与喹诺酮类耐药基因及16SrRNA甲基化酶基因高度相关,其耐药基因主要型别分别是qnrB,qnrS,qnrD和armA.

Microglia, a type of neuroglia, has a variety of functions such as phagocytosis, clearance, antigen presentation,promotion of repairment of injury and secretion of extracellular signaling molecules,in which phagocytosis of microglia plays a crucial role in maintaining brain tissue,remodeling synapses,clearance of several aberrant proteins such as amyloid β in neurodegenerative diseases, and in neurodevelopment. This review briefly summarizes the phagocytic function of microglia with underlying regulatory mechanism in neurodevelopment and neurodegenerative diseases,aiming to provide a new thought for the therapy of neurodegenerative diseases.

α-synuclein,a presynaptic protein,was found to be the major component of the lewy bodies in inherited and sporadic Parkinson's disease(PD).α-synuclein point mutations or genetic alteration can cause Parkinson's disease(PD).It is thought to be involved in the processes of neurodegeneration.This paper reviewed the toxic mechanisms of α-synuclein in Parkinson disease and α-synuclein transgenic animal models.

Objective To generate heart tissue specific Lrp2bp transgenic mouse and to study its effects on cardiomyopathy.Methods The transgenic plasmid was constructed by inserting the murine Lrp2bp gene into the downstream of α-MHC promoter.The transgenic mice were created by microinjection.The genotype of transgenic line was identified by PCR and the expression level of the gene was determined by Western blotting.The cardiac function and geometry were detected by echocardiography.The ultrastructural changes of cardiomyocytes from Lrp2bp transgenic mice were observed by transmission electron microscopy.Results Three lines of C57BL /6J transgenic mice with high level of Lrp2bp expression were identified from four transgenic founders.At 1 month old,the Lrp2bp transgenic mice showed increased thickness of the ventricular wall,dilated ventricular chamber,decreased ejection fraction and decreased fractional shortening compared with that of wild type mice.Conclusion Transgenic mice with cardiac tissue specific Lrp2bp gene have been established successfully and Lrp2bp caused compensation effect on the cardiomyopathy in the transgenic mice.