| 研究実績の概要 |
We completed three years of this research with another year for some critical data analysis. We systematically investigated the effects of landiolol in multiple organ dysfunctions in sepsis. Morphologically, landiolol hydrochloride, an ultra-short-acting β-blocker, plays a vital role in lessening LPS-induced cardiac, lung, kidney, and liver injury. We used male Wistar rats at 8 weeks of age and were administered with either saline or lipopolysaccharide (LPS) for three hours (3h), and some of the LPS-administered rats were continuously treated with landiolol for 3h, extending experiments for 6h and 10h. We have seen the changes in both circulatory and tissue TNF-α and IL-6 with alteration of the level of angiopoietin-2 in the organs mentioned above. At the same time, these changes were accompanied by LPS-induced considerable alteration in VEGF signaling with blood gas parameters. Here, we found that treating LPS-administered rats with landiolol starting from 3h significantly stopped the progression of damage to various organs with the normalization of angiopoietin-2. This treatment also considerably normalized blood gas parameters and tissue VEGF levels. Our data indicate that landiolol treatment in LPS-administered rats plays an essential role in attenuating organ damage through modulation of angiopoietin-2 with concomitant reversal of VEGF signaling.
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