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Objective To explore the neuroprotective effect and mechanism of picroside II on p38 mitogen activated protein kinase (p38 MAPK) signal transduction pathway after cerebral ischemia/reperfusion injury in rats. Methods A total of 150 healthy male Wistar rats were subject to establish middle cerebral artery occlusion/reperfusion (MCAO/R) models by inserting a monofilament thread. All rats were randomly divided into sham group, model group, picroside (Pier) group, anisomycin (Anis, agonist of p38 MAPK) group, Anis+Picr group, SB203580 (SB, inhibitor of p38 MAPK) group and SB+Picr group. The neurobehavioral function was evaluated by modified neurological severity score points (mNSS) test. The structure of neuron was observed using HE staining. The apoptotic cells were counted using TUNEL assay. The expression of phosphorylated p38 MAPK (p-p38 MAPK) in cortex was determined using the immunohistochemistry. And the expressions of p-p38 MAPK, phosphorylated MAPK activated protein kinase-2 (p-MK2), phosphorylated cytoplasm phospholipase A2 (p-cPLA2), interleukin-6 (IL-6) and tumor necrotic factor a (TNF-α) were determined by Western blotting. Results No neurological behavioral malfunction was found in sham group. In model group, the damage of neuron was worsened, while the neurobehavioral function score, apoptotic cell index and the expressions of p-p38 MAPK, p-MK2, p-cPLA2,IL-6 and TNF-α increased significantly than those in control group. No significant difference was found in TNF-α. In Pier group, SB group and SB+Picr group, the damage of neuron was lighter, the neurological behavioral function was improved, the number of apoptotic cells and the expressions of p-p38 MAPK, p- MK2, p-cPLA2 and IL-6 decreased significantly than those in model group. In Anis group and Anis + Pier group, the damage was worsen, the cerebral infarction was larger, and the expressions of p-p38 MAPK, p-MK2, p-cPLA2 and IL-6 increased significantly than those in control group. Conclusion Picroside II can protect the neuron from the apoptosis and inflammation reaction after MCAO/R by inhibiting p38 MAPK signal transduction pathway in rats.
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Background and purpose:P38 mitogen-activated protein kinase (P38MAPK) signal transduction pathway is involved in occurrence, development and transfer process in a wide variety of tumors. Urokinase-type plasminogen activator (uPA) plays an important role in tumor invasion and metastasis. This study aimed to explore the clinical signiifcance of the P38MAPK signaling pathway and the expression of uPA in ovarian cancer.Methods:The expressions of uPA, P38MAPK, ERK and AKT were detected in 49 cases of cervical adenocarcinoma by immunohistochemistry. The expressions of uPA and P38MAPK were detected by Western blot in ovarian cancer cell lines HO8910, HO-8910PM, SKOV3 and CAOV3. The changes of uPA and P38MAPK were detected by SB203580, a speciifc inhibitor of P38MAPK signal transduction pathway.Results:The result of immunohistochemical method showed that positive expression rates for uPA, P38MAPK, ERK and AKT were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of the uPA was positively correlated with the P38MAPK (r=0.865,P=0.001), and related with clinicopathologic stage, differentiated degree, lymph node metastasis, but not related with age and histologic type (P>0.05). The expressions of AKT and ERK were related with the lymph node metastasis and greater omentum metastasis(P0.05). The expression of uPA in HO-8910PM was higher than that in ovarian cancer cell lines HO8910, SKOV3 and CAOV3, and the expression of uPA reduced when the P38MAPK signal transduction pathway was cut off by the SB203580. The expressions of P38MAPK and uPA were negatively correlated with the prognosis of ovarian cancer (Log-rank=3.897 and 11.044,P=0.048 and 0.001). Conclusion:The P38MAPK signal transduction pathway was activated in ovarian cancer. The activated P38MAPK signal transduction pathway can raise the expression of uPA, which may contribute to the development of ovarian cancer. The result indicates that the P38MAPK signal transduction pathway and uPA might play an important role in the invasion and metastasis of ovarian cancer. P38MAPK and uPA might be useful markers for evaluating prognosis of ovarian cancer.