Effects of Shen-Fu Injection (参附注射液) on Apoptosis of Regulatory T Lymphocytes in Spleen during Post-Resuscitation Immune Dysfunction in A Porcine Model of Cardiac Arrest

Objective： To investigate whether Shen-Fu Injection（参附注射液, SFI） reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes（Treg） in the spleen. Methods： After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine（EP） group, and saline（SA） group（8 in each group）, which received central venous injection of SFI（1.0 m L/kg）, EP（0.02 mg/kg） and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated（sham） group（n=6）. After successful return of spontaneous circulation（ROSC）, apoptosis rate of splenic Treg was detected by flow cytometry; and the m RNA expression of forkhead/winged helix transcription factor（Foxp3） of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4（IL-4） and interferon-γ（IFN-γ） in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay（ELISA）. Results： Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 m RNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group（P〈0.05 or P〈0.01）. Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 m RNA expression, IFN-γ and IFN-γ/IL-4（P〈0.05）. Conclusions： SFI has significant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.

Ginseng-Derived Panaxadiol Saponins Promote Hematopoiesis Recovery in Cyclophosphamide-Induced Myelosuppressive Mice:Potential Novel Treatment of Chemotherapy-Induced Cytopenias

Objective：To investigate the potential efficacy of panaxadiol saponins component（PDS-C）,a biologically active fraction isolated from total ginsenosides,to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide（CTX）.Methods：Mice with myelosuppression induced by CTX were treated with PDS-C at a low-（20 mg/kg）,moderate-（40 mg/kg）,or high-dose（80 mg/kg） for 7 consecutive days.The level of peripheral white blood cell（WBC）,neutrophil（NEU） and platelet（PLT） were measured,the histopathology and colony formation were observed,the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot.Results：In response to PDS-C therapy,the peripheral WBC,NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner.Similarly,bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells（P〈0.01）.PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice,as evidenced by significantly increase in colony formation units-granulocytes/monocytes and-megakaryocytes（P〈0.01）.The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway,this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase（p-MEK） and extracellular signal-regulated kinases（p-ERK）,and receptor tyrosine kinase（C-kit） and globin transcription factor 1（GATA-1） in hematopoietic cells of CTX-treated mice（P〈0.05）.Conclusions：PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice,probably mediated by a mechanism involving MEK and ERK protein kinases,and C-kit and GATA-1 transcription factors.PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.