冠状动脉微循环功能障碍动物模型及中医药防治研究进展

冠状动脉微循环功能障碍(CMD)是心脏X综合征、经皮冠状动脉介入治疗(PCI)后无复流等微循环病变的共同发病机制。随着现代影像学的迅速发展,CMD的发生和防治得到越来越多的关注。CMD动物模型是研究疾病发病机制及评价药物作用的必不可少的工具,选择合适的CMD动物模型建立方法是开展CMD实验研究首先面临的问题。临床及实验研究显示,中医药在CMD的防治方面具有一定的特色。如何进一步阐明中药作用机制寻求最佳的中西医结合治疗方案,将是中医药干预CMD的研究重点。该文将从冠状动脉微循环障碍动物模型的建立评价方法及中医药防治冠状动脉微血管环障碍的研究进展进行综述,旨为冠状动脉微循环障碍实验及中医药的实验研究提供参考。     

中药香菊胶囊对初发性生殖器疱疹豚鼠模型的影响

目的:探讨中药香菊胶囊对生殖器疱疹(GH)豚鼠模型的影响。方法:选取Hartley雌性豚鼠30只,随机选取其中5只作为正常对照组,其余25只以人工感染单纯疱疹病毒2型(HSV-2)的方式建立GH动物模型,并随机分为模型对照组、阿昔洛韦组和香菊胶囊高、中、低剂量组,各组分别灌胃给药及给生理盐水后观察豚鼠发病情况和病程变化情况。结果:香菊胶囊治疗后GH豚鼠的皮损严重程度和消退时间较对照组明显降低,其中高剂量组效果最好,类似于阿昔洛韦组的用药效果,低剂量组效果最弱,中剂量组效果居中。香菊胶囊各剂量组豚鼠阴道内病毒滴度与阿昔洛韦组比较差异无统计学意义(P0.05)。结论:香菊胶囊能够抗HSV-2增殖,在豚鼠体内具有良好的抗HSV-2感染所致GH的作用。     

归甲疏通胶囊对大鼠离体子宫平滑肌收缩的影响

目的:观察归甲疏通胶囊对大鼠离体子宫平滑肌收缩的影响。选用健康未孕雌性成年大鼠40只,随机分为正常对照组,缩宫素模型组,归甲疏通胶囊高、中、低剂量组,除空白对照组外其他各组均采用缩宫素注射液人工造成动情期,以提高子宫敏感性。实验时处死大鼠并取出子宫,置于不同浓度的归甲疏通胶囊混悬液中,观察各组离体子宫张力、收缩强度、频率和活动力。结果:大鼠离体子宫平滑肌张力、强度、频率、活动力等指标,缩宫素模型对照组,归甲疏通胶囊高、中、低剂量组与空白对照组比较,差异均有统计学意义(P0.05);归甲疏通胶囊高、中、低剂量组与缩宫素模型对照组比较,差异均有统计学意义(P0.05);归甲疏通胶囊高、中、低剂量组组间比较差异也有统计学意义(P0.05)。大鼠离体子宫平滑肌张力、强度、频率、活动力等指标随着用药时间的延长逐渐降低。其中强度、频率、活动力用药各组用药10分钟、20分钟、30分钟时两两比较,差异均有统计学意义(P0.05)。大鼠离体子宫平滑肌张力归甲疏通胶囊高、中剂量组,用药10分钟、20分钟、30分钟时两两比较,差异均无统计学意义(P0.05);缩宫素模型对照组和归甲疏通胶囊低剂量组,用药10分钟时与用药20分钟、30分钟时比较,差异均有统计学意义(P0.05);用药20分钟时与用药30分钟时比较,差异也均有统计学意义(P0.05)。结论:归甲疏通胶囊可对抗缩宫素致大鼠离体子宫平滑肌的收缩,且有一定量效关系和时效关系。     

原发免疫性血小板减少症动物模型研究进展

原发免疫性血小板减少症(ITP)是一种以血小板减少、伴或不伴皮肤黏膜瘀紫、鼻衄、内脏出血等为特征的自身免疫性疾病,ITP动物模型是深入研究ITP发病机制与治疗方法的主要手段,在ITP的研究中一直发挥着重要作用。因此,如何制备与临床接近的动物模型是ITP研究领域的关键问题。目前原发免疫性血小板减少症动物模型的研究方法众多,主要有免疫造模、自发免疫模型、转基因造模以及其他造模方法。免疫造模是最常用的方法,实验用动物主要是小鼠,常用的注射途径是腹腔注射,常用的免疫原有抗血小板血清、单克隆/多克隆抗体、血小板等,自发模型与转基因模型比较少用。此外也有结合中医理论开展病证结合模型的研究,主要有ITP热盛证模型,ITP肾阴虚证模型,ITP气不摄血证模型等,为该病的证候研究提供了基础。本文对近些年来ITP疾病、病证结合动物模型的研究进展进行了比较系统的分析与总结,希望对该疾病的动物模型的进一步研究提供参考。     

Synergistic virulence of Porphyromonas gingivalis and Treponema denticola in a murine periodontitis model

Chronic periodontitis is characterized by the destruction of the tissues supporting the teeth and has been associated with the presence of a subgingival polymicrobial biofilm containing Porphyromonas gingivalis and Treponema denticola. We have investigated the potential synergistic virulence of P. gingivalis and T. denticola using a murine experimental model of periodontitis. An inoculation regime of four intra-oral doses of 1 × 10(10) P. gingivalis cells induced significant periodontal bone loss compared with loss in sham-inoculated mice, whereas doses of 1 × 10(9) cells or lower did not induce bone loss. Inoculation with T. denticola with up to eight doses of 1 × 10(10) cells failed to induce bone loss in this model. However, four doses of a co-inoculum of a 1 : 1 ratio of P. gingivalis and T. denticola at 5 × 10(8) or 1 × 10(9) total bacterial cells induced the same level of bone loss as four doses of 1 × 10(10) P. gingivalis cells. Co-inoculation induced strong P. gingivalis-specific T-cell proliferative and interferon-γ-dominant cytokine responses, and induced a strong T. denticola-specific interferon-γ dominant cytokine response. Only at the higher co-inoculum dose of 1 × 10(10) total cells was a T. denticola-specific T-cell proliferative response observed. These data show that P. gingivalis and T. denticola act synergistically to stimulate the host immune response and to induce alveolar bone loss in a murine experimental periodontitis model.     

Contribution of the periosteum to bone formation in guided bone regeneration. A study in monkeys

The periosteum has been referred to as a protective barrier in the regeneration of bone defects. The objective of this study was to determine the contribution of periosteum as a natural barrier to bone formation in guided bone regeneration. Mucoperiosteal flaps were elevated bilaterally on the buccal aspect of the mandibular angle in 5 cynomolgus monkeys. Bleeding was induced by perforating the cortical bone. A hemispherical titanium mesh was fixed over the areas thus creating a void 5 mm in height between the mesh and the bone surface. One one side the mesh was covered with an ePTFE membrane (test side). The contralateral side did not receive further treatment (control side). After 4 month healing, histomorphometric analyses were used to determine the percentage of new bone in the void underneath the mesh, and the ratio between mineralized tissue and marrow spaces in new and old bone. The mean percentage of new bone tissue was 77.2 +/- 7.5% for the test sides and 68.6 +/- 8.4% for the control sides (P = 0.018, t-test). This new bone contained 80.0 +/- 3.6% mineralized tissue in the test group and 82.5 +/- 5.0% in the control group (P > 0.05, t-test). In both groups the newly formed bone exhibited significantly less mineralized tissue than the old bone (P < 0.05, t-test). It is concluded from this study that new bone formation was enhanced by the additional use of an ePTFE membrane under a periosteum-lined mucoperiosteal flap when space maintenance was excluded as a critical factor.     

兔颞下颌关节盘移位与骨关节病关系的评价

目的评价颞下颌关节盘移位与骨关节病的关系。方法通过手术方法将２５只大耳白兔的颞下颌关节盘前移，术后１、２、４、８、１２周进行组织病理学检查。结果１１侧手术关节为部分关节盘前移位，８侧为完全性关节盘前移位，６侧为关节盘穿孔。部分关节盘前移位出现早期退行性改变和后期生理性改建，完全性关节盘前移位和关节盘穿孔出现退行性改变和严重的骨关节病。结论颞下颌关节盘前移位的程度与骨关节病有关，关节盘前移位越明显，越易出现骨关节病     

~(125)I标记抗Flt4多抗的制备及对淋巴结定位的动物实验

目的　研究氯胺T法标记兔抗鼠血管内皮生长因子受体 3的多克隆抗体 (Flt4PcAb) ,以此探索Flt4PcAb对体内淋巴结的导向定位能力 ,旨在为前哨淋巴结 (sentinellymphnode,SLN)的特异性定位提供实验依据。方法　应用氯胺T法对Flt4PcAb行12 5I标记 ,对标记产物行性质鉴定并进行大鼠体内导向定位实验。结果　标记率为 39.5 % ,标记产物比活度为 1.75MBq/μg ,放化纯度为 95 .4 % ;标记产物性质稳定 ,无热源 ;动物实验显示淋巴结与血液及各脏器单位重量的放射性比值较高。结论　Flt4PcAb具有良好的淋巴结的导向定位能力 ,是探索SLN准确定位的新途径。     

应用植入控释系统进行一次法根管治疗术的动物实验研究

目的：利用自制含氯霉素、甲硝唑等药物的控释系统，对实验家兔的血药浓度、药物抗菌活性和家兔根管、尖周组织的病理观察，为今后临床应用提供理论和实验依据。方法：应用组织病理观察和液相色谱分析技术。结果：用ＨＰＬＣ法得出实验用家兔血药浓度和抗菌活性均为阴性，根管及尖周组织病理切片无特殊表现。结论：自制控释系统是一种无毒、无副作用、有效的根管治疗药物剂型，可进行临床应用。     

Genetic variation in the recognition of Porphyromonas gingivalis antigens in mice

T-cell cytokine profiles, anti-Porphyromonas gingivalis antibodies and Western blot analysis of antibody responses were examined in BALB/c, CBA/CaH, C57BL6 and DBA/2J mice immunized intraperitoneally with different doses of P. gingivalis outer membrane antigens. Splenic CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma and IL-10 by FACS analysis and levels of anti-P. gingivalis antibodies in the serum samples determined by enzyme-linked immunosorbent assay. Western blot analysis was performed on the sera from mice immunized with 100 microg of P. gingivalis antigens. The four strains of mice demonstrated varying degrees of T-cell immunity, although the T-cell cytokine profiles exhibited by each strain were not affected by different immunizing doses. While BALB/c and DBA/2J mice exhibited responses that peaked at immunizing doses of 100-200 microg of P. gingivalis antigens, CBA/CaH and C57BL6 demonstrated weak T-cell responsiveness compared with control mice. Like the T-cell responses, serum antibody levels were not dose dependent. DBA/2J exhibited the lowest levels of anti-P. gingivalis antibodies followed by BALB/c with CBA/CaH and C57BL6 mice demonstrating the highest levels. Western blot analysis showed that there were differences in reactivity between the strains to a group of 13 antigens ranging in molecular weight from 15 to 43 kDa. Antibody responses to a number of these bands in BALB/c mice were of low density, whereas CBA/CaH and C57BL6 mice demonstrated high-density bands and DBA/2J mice showed medium to high responses. In conclusion, different immunizing doses of P. gingivalis outer membrane antigens had little effect on the T-cell cytokine responses and serum anti-P. gingivalis antibody levels. Western blot analysis, however, indicated that the four strains of mice exhibited different reactivity to some lower-molecular-weight antigens. Future studies are required to determine the significance of these differences, which may affect the outcome of P. gingivalis infection.