Effects of intracerebral hemorrhage and subsequent minimally invasive hematoma aspiration on expression of apoptosisrelated genes in rats

This study was to investigate the effects of intracerebral hemorrhage (ICH) and subsequent minimally invasive hematoma aspiration on the expression of apoptosis-related genes in rats. IV-collagenase was injected to the caudate nucleus of the rats to make ICH models. In the control group, 30 Sprague-Dawley (SD) rats were mock treated with saline instead of collagenase. Thirty SD rats with successful modeling were designated as the ICH group. Twenty-five SD rats with successful modeling and subsequent minimally invasive hematoma aspiration were designated as the therapy group. Expression of heat shock protein 70 (Hsp70), B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the brain tissues was detected by immunohistochemical assays. The expression of Hsp70, Bcl-2 and Bax in the control group was very low, and significantly increased in the ICH group and the therapy group. At each indicated time point, Hsp70 expression in the therapy group was significantly lower than that of the ICH group, Bax expression in the therapy group was significantly lower than that of the ICH group and Bcl-2 expression in the therapy group was significantly higher than that of the ICH group. These results suggest that ICH led to increased expression of apoptosis-related genes in the brain tissues. Hematoma aspiration up-regulated ICH induced Bcl-2 expression while down-regulated ICH induced Hsp70 and Bax expression.     

脂氧素 A4预处理对糖尿病大鼠心肌缺血再灌注时Caspase －3、Bcl －2和 Bax 表达的影响

目的：观察脂氧素 A4预处理对链尿佐菌素诱导的糖尿病大鼠心肌缺血再灌注时 Caspase －3、Bcl －2和 Bax 表达的影响。方法雄性 SD 大鼠60只,随机分为 CS、CI／R、CLX、DS、DI／R、DLX 组共6组（n ＝10）。 CS、CI／R、CLX组采用腹腔注射链尿佐菌素55 mg／kg 制备糖尿病模型。 CI／R、DI／R组建立大鼠心肌缺血再灌注模型,结扎冠脉左前降支30 min,CS 组和 DS 组仅穿线不结扎,CI／R组和 DI／R组缺血前5 min 经股静脉注射2 mL／kg 生理盐水,CLX组和 DLX组缺血前5 min 经股静脉注射脂氧素 A42.5μg／kg。再灌注4 h 时处死大鼠,取心肌组织,采用 HE 染色法光镜下观察缺血心肌组织形态学改变,通过 RT －PCR 和 Western blot 法检测缺血心肌 Caspase －3、Bcl －2和 Bax的表达水平,并计算 Bcl －2与 Bax 表达的比值（Bcl －2／Bax）。结果CLX组和 DLX组心肌组织病理学损伤较 CI／R组和 DI／R组减轻,Caspase －3和 Bax 的表达量减少,Bcl －2的表达量增加,Bcl －2／Bax 比值升高（P ＜0.05）。结论脂氧素 A4预处理能够下调糖尿病大鼠心肌缺血再灌注时 Caspase －3和 Bax 的表达,上调 Bcl －2的表达,使 Bcl －2／Bax 比值升高。     

大鼠脑出血周边组织脑水含量、细胞凋亡和Bax表达的变化及粒细胞集落刺激因子的影响

目的研究粒细胞集落刺激因子(G-CSF)对脑出血(ICH)大鼠神经功能损伤、脑水肿的影响,粒细胞集落刺激因子对大鼠脑出血周边组织Bax表达及细胞凋亡的影响。方法 Wistar大鼠112只,随机分为脑出血组、脑出血+G-CSF组,两组各分为(出血前、出血后4 h、6 h、12 h、24 h、72 h、7 d)7个时间点。免疫组化法测定大鼠脑出血周边组织Bax的表达,利用原位末端标记法测定出血周边组织中神经细胞的凋亡情况。并在脑出血后24 h、48 h、72 h、7 d测定大鼠神经功能评分和脑含水量。结果脑出血后24 h开始大鼠就出现明显的神经功能缺失症状,G-CSF治疗后神经功能缺失症状得到明显改善,在1 w内的各个时间点两组比较差异有显著性(P<0.01)。脑出血大鼠24 h即出现脑水肿,脑水肿形成的高峰时间在ICH后48 h~7 d左右,ICH大鼠在G-CSF治疗后脑水肿形成明显减轻,两组间比较差异有显著性(P<0.05;P<0.01)。大鼠脑出血周边组织Bax表达4 h开始升高(P<0.01),大约24 h左右Bax表达达峰值。大鼠脑出血周边组织6 h出现凋亡细胞,12 h上升显著(P<0.01),3 d达峰值,7 d时仍存在较多凋亡细胞。G-CSF干预后,Bax表达及凋亡细胞数量与脑出血组对应时间点比较显著下降(P<0.01)。结论脑出血大鼠出现明显脑水肿和神经功能损伤,脑出血周边组织神经细胞存在长时间凋亡。G-CSF可抑制大鼠脑出血后Bax蛋白表达,从而抑制神经细胞凋亡。     

单纯性胰腺创伤后大鼠胰腺细胞增殖状况的实验研究

目的：构建大鼠单纯性胰腺创伤模型观察胰腺细胞增殖变化特点并探讨胰腺细胞增殖与组织损伤的关系。方法将60只Wistar大鼠分为2组：撞击组（采用BIM‐Ⅲ生物撞击机构建胰腺创伤大鼠模型,40只）和对照组（假手术组,20只）,每组大鼠于建模后6、24、72 h ,7 d处死,采用分光光度法检测各组大鼠血清淀粉酶（AMS）、脂肪酶（LPS）活性,通过TUNEL染色和流式细胞技术测定胰腺组织细胞死亡并分析细胞周期分布特点,Western blot测定胰腺组织Bcl‐2、Bax蛋白的表达。结果撞击组大鼠LPS活性升高时相点晚于AMS且持续时间较长,TUNEL染色、流式细胞检测、Western blot结果揭示胰腺创伤可诱导胰腺组织细胞凋亡和代偿性增生。胰腺细胞增殖变化特点表明胰腺创伤后的最佳治疗时间是发病24 h内。结论同时检测AMS和L PS有助于判定胰腺的外分泌功能受损情况。     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

Bcl-2和Bax的表达与乳腺癌转移及预后的关系

目的　探讨Bcl 2和Bax基因在乳腺癌中的表达及与乳腺癌淋巴结转移、预后的关系。方法　应用SP免疫组化染色方法 ,检测 4 0例乳腺癌组织中Bcl 2、Bax的表达情况。结果　无淋巴结转移组Bcl 2阳性表达率与淋巴结转移组有显著差异 (P <0 .0 5 ) ,10年以上存活组Bcl 2阳性表达率与 10年以下存活组有显著差异 (P <0 .0 1)。无淋巴结转移组Bax阳性表达率与淋巴结转移组有显著差异 (P <0 .0 5 ) ,10年以上存活组Bax阳性表达率与 10年以下存活组有显著差异 (P <0 .0 5 )。结论　Bcl 2和Bax表达与乳腺癌淋巴结转移、预后关系密切 ,Bcl 2提示高表达、Bax低表达的乳腺癌患者有低的转移率及好的预后。     

葛根素诱导血管平滑肌细胞凋亡的实验研究

目的：观察葛根素促进人脐动脉血管平滑肌细胞凋亡的作用，探讨葛根素抑制平滑肌细胞增殖的机制。方法：分离培养人脐动脉平滑肌细胞，不同浓度葛根素与细胞孵育，TUNEL检测葛根素诱导细胞凋亡，rt-PCR实验检测促凋亡基因Bax和抗凋亡基因Bcl-XL。结果：随着葛根素浓度升高，细胞生长受抑制，TUNEL阳性细胞显著增加。rt-PCR实验发现促凋亡基因Bax随药物浓度和作用时间的增加而上升，而且Bax、Bcl-XL基因表达比例有一定升高。结论：葛根素通过调节经典的Bax、Bcl-XL通路对血管平滑肌细胞凋亡有一定诱导作用。     

Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells

AIM： To understand the role and significance of side population （SP） cells from hepatocellular carcinoma （HCC） in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells. METHODS： We used flow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97 and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium （MTT） assay and investigated the expression of p53, bcl-2 and bax genes during denutrition, by RT-PCR and immunofluorescence staining. RESULTS： The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively. SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells. CONCLUSION： It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the field of anticancer therapy.