肿瘤坏死因子、更生霉素和干扰素-γ联合应用对人卵巢癌裸鼠模型的协同作用

目的：研究联合应用肿瘤坏死因子（TNF）、干扰素－γ（IFN－γ）和更生霉素（KSM）对人卵巢癌裸鼠模型的协同作用。方法：将荷瘤裸鼠随机分成4组，分别用生理盐水、KSM、TNF＋IFN－γ、KSM＋TNF＋IFN－γ处理，观察肿瘤生长情况。结果：各组肿瘤相对体积比较，KSM组和KSM＋TNF＋IFN－γ组与对照组比较，差异有显著性（P＜0．05和P＜0．01）；TNF＋IFN－γ组与对照组比较，差异无显著性（P＞0．05），而KSM＋TNF＋IFN－γ组与KSM组比较，差异有显著性（P＜0．05）。结论：KSM与TNF、IFN－γ联合应用有协同抗卵巢癌细胞系3AO的作用，为临床应用提供了理论依据。     

低氧刺激鼻息肉黏膜上皮细胞炎性因子变化的初探

目的:研究低氧刺激慢性鼻窦炎伴鼻息肉（CRSwNP）与正常鼻黏膜上皮细胞炎性因子的变化与异同,探讨其在CRSwNP发病机制中的作用。方法:选择2015年6月至2018年1月在吉林大学中日联谊医院就诊的68例CRSwNP患者,其中男性36例,女性32例,年龄（45.2±12.5）岁（ xˉ±s,下同）,患者的...     

异氟烷对幼小鼠自主活动和学习记忆行为的影响

目的观察异氟烷(Iso)对幼小鼠自主活动和学习记忆行为的影响,探讨其与γ-氨基丁酸A受体(GABAA)的关系。方法 360只小鼠分为3大组,分别进行自主活动实验、避暗实验和跳台实验,每大组按分层随机区组设计分为正常对照组,Iso 0.05,0.1和0.2 ml·kg-1组、GABAA受体特异性阻断剂一叶萩碱(Sec)2,4和8 mg.kg-1组和Iso 0.2 m.lkg-1+Sec 2,4和8 mg.kg-1组。小鼠sc给予Sec 10 min后,再ip给予Iso,测试给药后15,30,45和60 min小鼠5 min内活动次数;跳台仪和避暗仪记录小鼠步入、跳下的潜伏期和错误次数。结果与同一时间点的正常对照组相比,Iso可减少小鼠自主活动次数,给予Iso后1 d小鼠避暗实验和跳台实验的步入和跳下潜伏期缩短以及错误次数增加(P<0.05)。正常小鼠单独给Sec(除Sec 8 mg·kg-1组15 min外)对小鼠自主活动、步入和跳下潜伏期和错误次数无明显影响,但Sec可改善Iso导致的小鼠自主活动次数,拮抗Iso对小鼠自主活动的影响,但随着时间延长拮抗作用逐渐减弱,明显低于正常对照组(P<0.05)。Sec延长Iso小鼠的跳下和步入潜伏期,减少错误次数,基本恢复至正常对照组水平,明显改善Iso对幼小鼠学习记忆的影响(P<0.05)。结论 Iso可降低幼小鼠自主活动次数,损害学习记忆能力,GABAA受体可能部分参与了以上作用。     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

去甲斑蝥素对G422脑胶质瘤抑制作用的体内研究

目的:研究去甲斑蝥素(NCTD)体内对脑胶质瘤G422细胞的抑制作用。方法:建立G422细胞小鼠移植瘤模型,将荷瘤小鼠随机分为模型组、CTX阳性对照组及NCTD高、中、低剂量组(100、50、25 mg.kg-1),每组10只,另设10只为正常对照组,正常对照组每日给生理盐水灌胃,CTX和NCTD组采用腹腔注射方式给药,10 d后双抗体夹心ABC-ELISA法测sIL-2R的含量;酶联免疫ELISA法测IFN-γ含量;剥瘤,计算抑瘤率;剥瘤的同时取脾脏,计算脾脏指数;MTT法检测NCTD对荷瘤小鼠脾脏T、B淋巴细胞增殖的影响。结果:NCTD可降低荷瘤小鼠血清sIL-2R含量,提高IFN-γ含量,抑制G422细胞小鼠移植瘤的生长;对脾脏指数影响较少,可促进荷瘤小鼠的T、B淋巴细胞增殖。结论:NCTD体内外可抑制G422细胞生长,并具有免疫调节作用。     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

人参三七川芎提取物对增龄和高血压大鼠血管平滑肌细胞的影响

目的 观察和比较增龄与高血压对大鼠主动脉血管平滑肌细胞(vascular smooth muscle cells,VSMCs)的影响及人参、三七、川芎提取物的干预作用。方法 采用原代细胞培养的方法建立大鼠主动脉VSMCs模型,其中增龄实验分5组：青年对照组(Yon组)、老龄组(Old组)、老龄+普罗布考组(Old+Pro组)、老龄+中药低剂量组(Old+Low组)和老龄+中药高剂量组(Old+High组);高血压实验分5组：Wistar-Kyoto对照组(WKY组)、自发性高血压大鼠(spontaneously hypertensive rat,SHR)组、SHR+缬沙坦组(SHR+Val组)、SHR+中药低剂量组(SHR+Low组)和SHR+中药高剂量组(SHR +High组)。采用MTT法检测细胞增殖,免疫细胞化学法检测基质金属蛋白酶-9(MMP-9)表达,RT-PCR和Western blot分别检测过氧化物酶增殖物激活受体γ(peroxisome proliferator activated receptor-γ,PPAR-γ)mRNA和蛋白表达。结果 与Yon组比较,Old组VSMCs增殖水平和MMP-9表达升高,PPAR-γ mRNA和蛋白表达减少,差异均有统计学意义(P<0.05)。与Old组比较,Old+Pro组、Old+High组和 Old+Low组VSMCs增殖水平和MMP-9表达明显降低,PPAR-γ mRNA表达明显增加(均P<0.05),Old+Pro组和Old+Low组PPAR-γ蛋白表达明显增加(均P<0.05)。与WKY组比较,SHR组VSMCs增殖水平和MMP-9表达明显升高,PPAR-γ mRNA和蛋白表达明显减少(均P<0.05);与SHR组比较,SHR+Val组、SHR +High组和SHR+Low组VSMCs增殖水平和MMP-9表达明显降低,PPAR-γ mRNA和蛋白表达增加(均P<0.05)。结论 增龄和高血压均可造成大鼠主动脉VSMCs过度增殖及相关细胞活性因子的表达改变,中药人参、三七、川芎提取物能够降低其增殖水平,减少负性细胞因子的表达以降低增龄和高血压对VSMCs的损害,延缓血管细胞的老化。     

The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

The bark of Betula platyphylla Sukat. var. japonica Hara (Asian White Birch, AWB) is one of the herbs used in Eastern countries for the treatment of various inflammatory diseases including atopic dermatitis (AD). The present study was performed to examine if and how the bark of AWB inhibits the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PC). With this aim, we examined the skin symptom severity, itching behavior, serum immunoglobulin (Ig) E level and mRNA expression of cytokines at iliac and cervical lymph nodes in the mice. Oral administration of AWB extracts (25, 100 and 250 mg/kg) to the PC-treated mice inhibited the development of AD-like skin lesions as exemplified by a significant decrease in the total skin severity scores, itching behavior and a decrease in hypertrophy and infiltration of inflammatory cells into dermis. The serum IgE level was also significantly reduced by AWB extract. In the RT-PCR results, the expression of interleukin-4 mRNA was reduced by AWB extract, whereas the expression of interferon-gamma mRNA was not changed. These results suggest that AWB inhibits the development of AD-like skin lesions in NC/Nga mice through the suppression of the T-helper 2 cell response.     

Inhibition of pro-inflammatory mediators and tumor cell proliferation by Anisomeles indica extracts

Anisomeles indica (L.) Kuntze (Labiatae), is a traditional anti-inflammatory herb used in Taiwan. The aqueous and methanolic extracts of whole plants, leaves, flowers and stems; and chloroform and n-butanol fractions of methanol extract, from A. indica were investigated for their anti-inflammatory activity on murine peritoneal macrophages. In addition, the tumor cells proliferation inhibition activities of these extracts were also evaluated against a panel of tumor cell lines such as Colon 205, PC 3, HepG2 and MCF 7. Treatment with A. indica extracts did not reduce cell viability at any dose used. However, all the extracts significantly inhibited the enhanced production of NO radicals, and pro-inflammatory cytokines (TNF-alpha, and IL-12) induced by LPS/IFN-gamma in a dose-dependent manner. Furthermore, methanolic extracts of leaves and flowers significantly and dose-dependently arrest mitogen-stimulated spleen cells in G0/G1 stage, in addition to their cell proliferation inhibition against Colon 205, MCF 7 and PC 3 by 94, 82; 98, 71; 82, 98%, respectively, at 200 microg/mL concentration. This is the first report on A. indica extracts for their growth inhibitory activities, against inflammatory mediator production, and human tumor cell lines, colon, prostate, hepatoma and breast cells proliferation.