ABSTRACT
Objective To explore the role of apoptosis in the development of acute lung injury (ALI) after severe acute pancreatitis (SAP) and its mechanism via Notch/Hes signal transduction pathway in the pathologic process.Methods Fifty healthy male Sprague Dawley rats were randomly divided into,sham group (n=8) and model group (n=42).Tissue samples of model group were collected randomly at 3 (n=10),6 (n=10),12 (n=10) and 24h (n=12) after model establishment.Tissue collection of Sham group was conducted at 3h.Left lung wet/dry weight ratio (W/D) was calculated;Histological scores of pancreatic and lung tissues were assessed under microscope;myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) of lung tissues were determined by enzymatic-chemical method and radioimmunoassay method respectively.Apoptosis of lung cells was evaluated by TUNEL assay followed by calculation of apoptosis index.Protein levels of Notch-l,Hes-1 and Hes-5 were also detected semi-quantitatively by Western blotting.Results The lung tissue W/D of model rats exhibited a gradual increment at the prior 12 hours,and the ratio was significantly higher than that of sham group at each time point (P＜0.01) while it reached the peak at 12h time point.Pancreatic and lung pathological scores of model groups were increased at all time points and significantly higher than sham group (P＜0.01).Lung pathological scores of model groups achieved a peak at 12h.Meanwhile,lung MPO and TNF-α of model groups showed the same increment trend at each time points.The apoptosis index (AI) of lung cells in model groups were higher than that in sham group (P＜0.01).Compared with sham group,the model groups showed lower protein expression levels of Notch-1,especially at 3,6 and 12h (P＜0.05).Notch-1 protein expression level of 12h group was lower than that of 3,6 and 24h groups (P＜0.01).Correlation analysis found that apoptosis of lung cells was significantly negatively related to histopathological scores (r=-0.834,P＜0.01).The Notch-1 protein expression showed positive correlation with AI (r=0.515,P=0.004),but significantly negative correlation with W/D (r=-0.593,P=0.001),histological scores (r=-0.306,P=0.002),MPO (r=-0.687,P＜0.01) and TNF-α (r=-0.574,P=0.001) in the lung tissue.Conclusions Lung cell apoptosis,which is negatively correlated to tissue injury levels,may play an important role in the development of ALI after SAP.Inhibitory state of Notch-1 signaling transduction can aggravate ALI in the pathologic process.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of total saponins of Rubus parviflolius (TSRP) on brain edema and blood brain barrier in rats.</p><p><b>METHOD</b>The model of local cerebral ischemia was established in rats by reversible inserting a nylon thread into the anterior cerebral artery through the internal carotid artery brain hydrated amount and content change of Evan' s blue (EB) in cortex subjected to 2h middle cererbral artery occlusion (MACO) followed by 6 h, 24 h, 48 h, 72 h reperfusion and effect of TSRP. penetrability of blood brain-barrier (BBB) the index includes brain hydrated amount and penetrability of blood brain-barrier BBB.</p><p><b>RESULT</b>Com- pared with I/R group. Both brain hydrated amount and the EB content decreased significantly in TSRP groups on the 6 h, 24 h, 48 h, 72 h of reperfusion after 2 hour of cerebral ischemia induced by MACO model.</p><p><b>CONCLUSION</b>TSRP could decrease brain hydrated amount and markedly lower permeability of blood-brain barrier subjected to 2 h MACO followed by 24 h reperfusion, and this may be a mechanism of TSRP alleviating brain edema during I/R.</p>
Subject(s)
Animals , Male , Rats , Blood-Brain Barrier , Brain Edema , Drug Therapy , Pathology , Brain Ischemia , Infarction, Middle Cerebral Artery , Phytotherapy , Plants, Medicinal , Chemistry , Random Allocation , Rats, Sprague-Dawley , Reperfusion Injury , Rosaceae , Chemistry , Saponins , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To observe the protective effects of total glycosides Rubus parviflolius (TGRP) on local cerebral ischemic.</p><p><b>METHOD</b>The local cerebral ischemia in rat was made by middle cerebral artery occlusion(MACO). The infraction weight was determined by TTC stain. SOD, MDA, GSH and apoptotis were determined with different method respectively.</p><p><b>RESULT</b>TGRP 20, 10 mg x kg(-1) ig markedly improved the abnormal nervous symptoms, incredsed the SOD, GSH activity and reduced contentes of MDA in brain of MACO rat, TGRP 20 mg x kg(-1) ig significantly decreased the numbers of apoptotic cells in ischemic cortex.</p><p><b>CONCLUSION</b>TGRP has protective effects against cerebral infraction, and its mechanism may be related to anti-apoptotis and free radical.</p>