Ulinastatin promotes T lymphocyte apoptosis in rats with severe acute pancreatitis via mitochondrial pathways

Abstract

ABSTRACT. We explored the influence of ulinastatin on apoptosis of T lymphocytes in rats with severe acute pancreatitis (SAP) and the effect of ulinastatin on mitochondrial apoptosis pathways in spleen lymphocytes. Thirty-six Wistar rats were randomly divided into three groups (N = 12): a sham operated group, a SAP group, and an ulinastatin-treated SAP group. The SAP model was established by injecting 5% sodium taurocholate into the intrapancreatobiliary duct. Study rats were sacrificed after 24 h, and splenic lymphocytes were then collected. CD 4 + and CD 8 + T lymphocytes were labeled by direct immune fluorescence assays; the percentage of apoptotic cells, mitochondrial membrane potential levels, and mitochondria permeability transition pore opening levels were measured by flow cytometry. In the ulinastatin-treated SAP group, the ratio of CD 4 + /CD 8 + T lymphocytes was significantly higher than that in the SAP group, and the apoptosis percentage of CD 4 + T lymphocytes was significantly decreased. The percentage of lymphocytes with an abnormal opening of the mitochondrial permeability transition pore and lymphocytes C.L. Wang et al. 5512©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 5511-5518 (2015) with decreased mitochondrial membrane potential in the ulinastatintreated SAP group were significantly lower than that in the SAP group. Ulinastatin can directly enhance immunological function and attenuate immune suppression in SAP rats through inhibiting the apoptosis of CD 4 + T lymphocytes. These study findings demonstrate that therapeutic effects may occur through inhibiting the apoptosis induced by mitochondrial signaling pathways.

Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

“…Another study indicated that ulinastatin can enhance immunological function and reduce the injury in SAP rats through inhibiting the apoptosis of CD4 + T cells [17]. Hao et al [18] showed that UTI can attenuate inflammatory response of patients undergoing cardiopulmonary bypass by inducing the expansion of CD4 + CD25 + Tregs.…”

Retrospective analysis of the role of Ulinastatin in reducing mortality in severe pancreatitis in critical care unit in Nepal

“…Ulinastatin can enhance immunological function and reduce the injury in SAP rats by inhibiting the apoptosis of CD4+ T cells. [11] Another study by Yu Pan et al in the rat model showed a significant decrease in CD4+CD25+ T cells in the ulinastatin group. [12] this study demonstrated that in the SAP rat model, pro-inflammatory cytokines TNF-α and IL-1α and anti-inflammatory cytokine IL-10 all were increased significantly, while TGF-α was decreased and treatment of ulinastatin led to decreased levels of TNF-α, IL-1α, and increased level of IL-10, thus attenuated the acute inflammatory response and improved the survival rate in the SAP rats.…”

Pterostilbene as treatment for severe acute pancreatitis

“…A retrograde puncture was made on the biliary pancreatic duct via duodenal papilla. Subsequently, freshly prepared 5% sodium taurocholate solution (Sigma, USA) was perfused into the biliary pancreatic duct at 0.1 mL/min to reach an internal concentration of 0.1 mg/100 g as previously described (Wang et al, 2015b). The biliary duct was then clipped for 5 min to immerse all pancreatic lobes into sodium taurocholate solutions.…”