Mansy S S, Yehia H A, Hassan M M, Hassan E A, Youssef M M, Hadi A A, Mackenzie C D
Department of Electron Microscopy, Theodor Bilharz Research Institute, Imbaba Guiza, Egypt.
Arzneimittelforschung. 1998 Aug;48(8):855-61.
In clinical practice, octreotide (CAS 83150-76-9) has its greatest impact in the management of bleeding varices. The present work is the first one which was undertaken to investigate the possible use of octreotide as an antifibrotic agent and to study its effect on hepatic vasculature in Schistosoma mansoni infection. The material of this investigation consisted of two groups of albino mice (A, B), subdivided each into normal control, infected control, subgroups treated with octreotide, praziquantel (CAS 55268-74-1), and a combination of octreotide and praziquantel. Groups A and B were sacrificed at the 8th week and the 18th week post infection, respectively. By analysis of the obtained results, octreotide induced a reduction of the portal pressure, the weight of the spleen and the liver, the liver egg load (number of eggs) granuloma size and cellularity, and of the degree of hepatic fibrosis quantified by serum N-terminal peptide of type III procollagen in serum, serum laminin and tissue collagen using a Picrosirius red dye assay. Moreover, the biochemical state of hepatocytes has been improved. The subgroups treated with octreotide in association with praziquantel revealed better results than the subgroups treated with praziquantel alone. These obtained data were analysed in terms of histological extent of liver fibrosis in sections stained with Masson trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastructural level and by immunohistochemical demarcation of endothelial cells of blood vessels through the determination of factor VIII-related antigen. The promising results detected in this study may encourage to further investigate the positive findings of this drug with the intention of its possible application on a clinical level.
在临床实践中,奥曲肽(CAS 83150-76-9)在治疗静脉曲张出血方面具有最大的影响。本研究是首次探讨奥曲肽作为抗纤维化药物的可能用途,并研究其对曼氏血吸虫感染肝脏血管系统的影响。本研究材料包括两组白化小鼠(A组、B组),每组再细分为正常对照组、感染对照组、奥曲肽治疗亚组、吡喹酮(CAS 55268-74-1)治疗亚组以及奥曲肽与吡喹酮联合治疗亚组。A组和B组分别在感染后第8周和第18周处死。通过对所得结果的分析,奥曲肽可降低门静脉压力、脾脏和肝脏重量、肝卵负荷(卵数量)、肉芽肿大小和细胞数量,以及通过血清III型前胶原N端肽、血清层粘连蛋白和使用苦味酸天狼星红染色法测定的组织胶原蛋白来量化的肝纤维化程度。此外,肝细胞的生化状态得到改善。奥曲肽与吡喹酮联合治疗的亚组比单独使用吡喹酮治疗的亚组显示出更好的结果。这些所得数据通过用Masson三色染色和天狼星红染色的切片中肝纤维化的组织学范围、超微结构水平的肝细胞和窦状隙变化以及通过测定VIII因子相关抗原对血管内皮细胞进行免疫组织化学分界来分析。本研究中检测到的有前景的结果可能会鼓励进一步研究该药物的阳性发现,以期其可能在临床层面得到应用。