Effect Of CGA Derived Polypeptide CHR On Vascular Permeability Regulatory Organs In Sepsis Mice And The Clinical Efficacy Of Ulinastatin Combined With Xuebijing In The Treatment Of Sepsis

Objective:To explore the influence and possible mechanism of the CGA derived peptide CHR on vascular hyperpermeability in septic mice.Methods:Septic mice model was employed as the research object, then CHR was intraperitoneal injected in septic mice. The experiment was composed of control group, LPS 10mg/kg (model) group、CHR 0.016mg/kg +LPS 10mg/kg (CL) group and CHR 0.08mg/kg+LPS 10mg/kg (CH) group. After 6 h the mice’s anesthesia, the lung water was measured by wet/dry weight ratio,and vascular permeability was measured by Evans blue dye. Lung, liver and kidney tissue histological changements were displayed by tissue biopsies HE dying. The expression of VE-cad in lung, liver tissue was observated by immunohistochemistry.Results:1. The effect of CHR on lung wet/dry weight ratio in septic miceCompared with normal group, W/D ratio of lung tissue significantly increased in model group (5.2±0.265 vs 4.327±0.092 5.2, P=0.006). Compared with model group, the W/D ratio of lung tissue significantly reduced in CH group (4.423±0.057 vs.5.2±0.265, P=0.008), the W/D ratio of lung tissue reduced in CL group, but no statistically difference (4.807±0.067 vs 5.2±0.265 P=0.067).2. The effect of CHR of Evans blue permeability in septic miceCompared with normal group, the EB concentration of lung, liver and kidney tissues significantly increased in model group (1.860±0.46lμg/ml vs 1.077±0.142μg/ml,P=0.048;1.973±0.334μg/ml vs 1.19±0.12μg/ml,P= 0.02;1.917±0.164μg/ml vs 1.34±0.213μg/ml, p=0.021). Compared with model group, the EB concentration of lung and liver tissues significantly decreased in CH group (1.06±0.104μg/ml vs 1.860±0.461μg/ml, p=0.043; 0.94±0.493μg/ml vs 1.973±0.334μg/ml, P=0.03), the EB concentration of lung and liver tissues decreased in CL group (1.123±0.328μg/ml vs 1.860 ±0.461μg/ml,P=0.055; 1.733±0.104μg/ml vs 1.973±0.334μg/ml, p=0.38), but no statistically difference. Compared with model group, the EB concentration of kidney tissues decreased in CL group and CH group (1.873±0.415μg/ml vs 1.917±0.164μg/ml, p=0.879,1.66±0.235μg/ml vs 1.917±0.164 μg/ml, p=0.204), but no statistically difference.3. The effect of CHR on histomorphology of lung tissue, liver tissue and kidney tissue in septic mice.Compared with the normal group, we could see visible pink edematous fluid in alveolar cavities, alveolar wall destroyed, liver cell edema, hemorrhagic effusion around liver cell, hepatic cord disordered, capsular space diminished, hemorrhagic effusion around renal tubules and inflammatory cells infiltration in model group. Compared with model group, we can see all of the morphological changes of model group lightened in CH group and CL group, and these changements were more obvious in CH group.4. The effect of CHR on VE-cad expression of lung, liver tissues in septic mice.Compared with normal group, the expression of VE-cad in lung and liver tissue decreased in model group. Compared with model group, the expression of VE-cad in lung tissue significantly increased in CH group, the expression of VE-cad in liver tissue increased, but no statistically difference.Conclusion:CGA derived peptide CRH can improve the vascular permeability, reduce tissue edema and protect organs in septic mice, the regulating mechanism may be related to the increased expression of VE-cad in vascular endothelial cells.Objective:To evaluate the clinical effectiveness of ulinastation combined with Xuebijing for treating sepsis.Method:The database such as Cochrane library, Pubmed, CBM, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials(RCTs), and the relevant references of included studies were also retrieved. Studies were screened, data were extracted, and the methodological quality was assessed by two reviewers independently. Meta-analysis was conducted by using RevMan 5.2 software.Results:A total of 12 studies involving 876 participants(experimental group:449, control group:427) were included. The results showed that compared with the group of routine therapies and group of single administration of either Ulinastatin or Xuebijing, experimental group of Ulinastatin combined with Xuebijing was superior in the following aspects with significant differences:morality:RR=0.45,95%CI(0.35,0.59),7d APACHE II:MD=-4.91,95%CI(-6.83,-2.98).Conclusion:According to the domestic evidence, ulinastatin combined with Xuebijing for treating sepsis is superior to both the routine therapies and the single administration of either Ulinastatin or Xuebijing. It provides a new and prospective therapeutic method for sepsis. However, this conclusion has to be further verified by large scale and double blinded RCTs.