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OBJECTIVE: To synthesize low molecular weight chitosan-acetylcysteine (LMWC-NAC) conjugate and investigate its renal targeting profile and the rapeutic effects in model mice with acute kidney injury (AKI).METHODS: NAC was conjugated to LMWC by EDC/NHS reaction and the LMWC-NAC conjugate was identified by 1H-NMR. The cellular uptake of LMWC-NAC conjugate and megalin receptor involved in this process was investigated in vitro. In addition, the tissue distribution of ICG-labelled LMWC-NAC conjugate was investigated in nude mice. AKI were induced by LPS intraperitoneal injection (20 mg·kg-1).The parameters including Scr, BUN, inflammatory factors (TNF-α and IL-1β), and oxidative stress (MDA) were determined and renal histology was observed. RESULTS: LMWC-NAC conjugate was successfully synthesized by the amide interaction.The in vitrostudies demonstrated that the uptake of LMWC-NAC conjugate was mediated by the megalin receptor on HK-2 cells, and the tissue distribution experiment indicated that LMWC-NAC conjugate was mainly accumulated in the kidney.LMWC-NAC conjugate significantly suppressed Scr, BUN, inflammatory factors and oxidative stress (P<0.01) and improved kidney injury. CONCLUSION: LMWC-NAC conjugate showed good renal targeting profile and effect in recovering renal functions, which indicates the potential of LMWC-NAC conjugate as a safe and efficient drug delivery system for the treatment of AKI.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of immune modulation therapy on cardiac function and lymphocyte subsets in aged patients with chronic heart failure (CHF).</p><p><b>METHODS</b>CHF (NYHA classification: II-IV) patients older than 60 years were randomly divided into two groups: CHF intervention group received regular therapy and thymopetide (2 mg/day i.m. for 75 days, n = 48), CHF control group received regular therapy (n = 48), 45 healthy individuals older than 60 years served as normal control. Left ventricular ejection faction of (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), lymphocyte subsets, plasma high sensitive C-reactive protein (hsCRP), plasma brain natrium peptide (BNP) and 6 minutes walking distance (6MWT) were measured at before therapy, after the first course (15 days) of treatment and after the third course of treatment (75 days).</p><p><b>RESULTS</b>(1) Before therapy, the levels of BNP, hsCRP, CD8 T cells, LVEDD and LVESD were significantly higher and the levels of CD3, CD4, CD19 T cells, NK, CD4/CD8 ratio, LVEF and 6MWT were significantly lower in CHF patients compared to compared normal controls (all P < 0.05). These parameters were similar between CHF intervention group and CHF control group. (2) At 15 days, the levels of CD3, CD4, CD19 T cells and NK were significantly increased (P < 0.05 or P < 0.01) while the level of CD8, BNP and hsCRP were significantly decreased (P < 0.05 or P < 0.01) in CHF intervention group compared with CHF control group. (3) At 75 days, the levels of CD3, CD4, CD19 T cells, NK, CD4/CD8, LVEF and 6MWT were significantly increased (P < 0.05 or P < 0.01) while the levels of CD8, BNP, hsCRP and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were significantly decreased (P < 0.05 or P < 0.01) in CHF intervention group compared with CHF control group.</p><p><b>CONCLUSION</b>Thymopetide, an immune modulating agent, might regulate the quantity and proportion of lymphocyte subsets and improve cardiac function in aged patients with CHF, indicating that immune modulation therapy might be a new treatment strategy for aged CHF patients.</p>