Hansen M B, Tindholdt T T, Elbrønd V S, Makinde M, Cassuto J, Beubler E, Westerberg E J, Skadhauge E
Department of Anatomy and Physiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Pharmacol Toxicol. 1996 Feb;78(2):104-10. doi: 10.1111/j.1600-0773.1996.tb00189.x.
alpha-Trinositol (D-myo-inositol 1,2,6-trisphosphate, PP56) is a novel antiinflammatory drug. This study elucidates the effect of intravenous alpha-trinositol on basal and acute fluid transport and morphological changes following cholera toxin administration in pig jejunum in vivo. Using isolated jejunal tied-off loops, the fluid hypersecretory (accumulation) effect of different doses of cholera toxin was studied in pigs treated intravenously with saline added different doses (0, 4, 8, 16 and 32 mg x kg-1 x hr-1) of alpha-trinositol. Levels of alpha-trinositol, as well as stereomicroscopical, light microscopical and scanning electron microscopical morphological studies were performed. Cholera toxin evoked a dose-dependent fluid hypersecretion. Treatment with alpha-trinositol caused a dose-dependent inhibition of the cholera toxin-induced fluid hypersecretion and did not affect basal fluid absorption. The 16 mg x kg-1 x hr-1 alpha-trinositol dose gave a maximal inhibition of 36%. Morphological studies showed only minor changes following 6 hr of exposure to 20 micrograms x loop-1 cholera toxin. These changes consisted of dilation of the villus capillaries, an increase of apical membrane blebbing and a reduction of the intercellular space. Treatment with 16 mg x kg-1 x hr-1 alpha-trinositol alone did not induce any morphological changes, and did not alter the morphological changes induced by cholera toxin, which caused fluid hypersecretion and only minor acute morphological changes. In conclusion, alpha-trinositol treatment reduced cholera toxin-induced fluid hypersecretion without altering basal fluid absorption, basal morphology, or cholera toxin-induced morphological changes in pig jejunum in vivo.
α-三磷酸肌醇（D-肌醇1,2,6-三磷酸，PP56）是一种新型抗炎药物。本研究阐明了静脉注射α-三磷酸肌醇对猪空肠在体内给予霍乱毒素后基础和急性液体转运以及形态变化的影响。使用分离的空肠结扎环，在静脉注射添加不同剂量（0、4、8、16和32mg·kg⁻¹·hr⁻¹）α-三磷酸肌醇的猪中研究了不同剂量霍乱毒素的液体高分泌（积聚）效应。进行了α-三磷酸肌醇水平以及立体显微镜、光学显微镜和扫描电子显微镜形态学研究。霍乱毒素引起剂量依赖性的液体高分泌。α-三磷酸肌醇治疗导致霍乱毒素诱导的液体高分泌呈剂量依赖性抑制，且不影响基础液体吸收。16mg·kg⁻¹·hr⁻¹的α-三磷酸肌醇剂量产生了36%的最大抑制作用。形态学研究表明，在暴露于20μg·环⁻¹霍乱毒素6小时后仅出现轻微变化。这些变化包括绒毛毛细血管扩张、顶端膜泡形成增加和细胞间隙减小。单独使用16mg·kg⁻¹·hr⁻¹的α-三磷酸肌醇治疗未诱导任何形态学变化，也未改变霍乱毒素诱导的形态学变化，霍乱毒素引起液体高分泌且仅伴有轻微的急性形态学变化。总之，α-三磷酸肌醇治疗减少了霍乱毒素诱导的液体高分泌，而不改变猪空肠在体内的基础液体吸收、基础形态或霍乱毒素诱导的形态学变化。
