We investigated tte effects of Bukuryoshigyaku-to on cxperimental hemorrhagic shock. Twelve mongrel dogs, which were anesthetized with 26mg/kg of pentobarbital were used, Bukuryoshigyaku-to was given to six dogs and saline solution alone was given to six dogs as a control. Under artificial respiration management, a hemorrhagic shock model was created by modified Wiggers method. The drug was administered by enema immediately after the compensatory phase. Bukuryoshigyaku-to, consistied of 4g Bukuryo (Hoelen), 2g of Kanzo (Glycyrrhizae Radix), 2g Kankyo (Zingiberis Siccatum Rhizoma), 2g of Ninjin (Ginseng Radix) and 2g of Bushi (Aconiti Tuber), which were extracted by boiling for approximately 30 minutes.
The results showed no statistical differences in the changes in the mean arterial pressure and central venous pressure between the two groups. However, the cardiac index was significantly higher in the observation phase in the Bukuryoshigyaku-to group than in the control group. A drop in body pressure was prevented in the traditional Bukuryoshigyaku-to group.
These findings suggest the effectiveness of Bukuryoshigyaku-to in the treatment of hemorrhagic shock.

Animals ; Basic Helix-Loop-Helix Transcription Factors ; physiology ; Chronic Disease ; Humans ; Hypoxia ; complications ; Hypoxia-Inducible Factor 1 ; physiology ; Kidney ; metabolism ; Kidney Diseases ; etiology ; Oxidative Stress ; Procollagen-Proline Dioxygenase ; physiology

Background/Aims: Intestinal fibrosis is a major complication of Crohn’s disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. Methods: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. Results: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. Conclusions PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment.