Effects of 11, 12-EET and ischemic preconditioning on phosphorylated ERK and p38 MAPK during ischemia and reperfusion in rat myocardium

AIM: In order to study the relationship between the ERK and p38 MAPK activation and the protection of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) and ischemia preconditioning (IP), the effects of 11, 12-EET and ischemic preconditioning on phosphorylated ERK and p38 MAPK during ischemia and reperfusion in rat myocardium were examined. METHODS: The rat heart was subjected to ischemia for 5 min by ligating the left anterior descending coronary artery followed by reperfusion for 5 min (two times) to undergo ischemia preconditioning. The rats were divided into 5 groups: (1) control; (2) sham group; (3) ischemia/reperfusion (I/R) group, in which the rat heart suffered from 60 min ischemia followed by 30 min reperfusion; (4) IP plus I/R group; (5) EET plus I/R group, in which 6.28×10^-8 mol/L 11, 12-EET was injected intravenously 20 min before I/R. The heart function was examined, and phosphorylated ERK and p38 MAPK were detected by Western blot. RESULTS: At 30 min reperfusion, +dp/dt_max, -dp/dt_max and LVDP decreased significantly in I/R group compared with sham group, IP plus I/R group and EET plus I/R group; Phosphorylated ERK1/2 level was higher in I/R group than sham group, but was lower in I/R group than IP plus I/R group and EET plus I/R group; Phosphorylated p38 MAPK level was lower in control, sham, IP plus I/R and EET plus I/R group than I/R group. CONCLUSION: 11,12-EET protects rat heart against ischemia/reperfusion injury, the mechanism may be related to activation of ERK1/2 and inhibition of p38 MAPK.     

马立克氏病病毒pp38基因真核表达质粒的构建及其在鸡胚成纤维细胞中的表达

通过 PCR方法扩增马立克氏病病毒 (Marek′s disease virus,MDV) Md11株的 pp38基因 ,并将其克隆到真核表达载体 pc DNA3.1/ zeo( )中。阳性克隆鉴定后 ,在脂质体作用下转染鸡胚成纤维细胞 (CEF) ,通过间接免疫荧光试验 (IFA)检测到了 pp38在 CEF中的表达。     

Effects of Jiedu-Qingfei mixture on NF-κB and p38 MAPK pathways in lung tissues of rats with Mycoplasma pneumoniae infection

AIM: To observe the therapeutic effect of Jiedu-Qingfei mixture on Mycoplasma pneumoniae (MP)-infected rat lung tissues and to explore its mechanism. METHODS: SD rats (n=40) were randomly divided into 4 groups:blank control group, model group, Jiedu-Qingfei group and positive control group, with 10 rats in each group. The rats in experimental groups were slowly dripped with 1×10⁹ CFU/L MP solution into their nostrils for 4 d. One rat in each group was sacrificed for MP nucleic acid detection at the second day after inoculation, and the other rats were given gavage therapy. The rats in blank control group and model group were intragastrically given the same volume of normal saline, the rats in Jiedu-Qingfei group were given 8 mL/kg Jiedu-Qingfei mixture daily for 4 weeks, and the rats in psoitive control group were given dexmethasone sodium phosphate (0.5 mg·kg^-1·d^-1). After the experiment, the rats were killed. The serum and bronchoalveolar lavage fluid (BALF) were collected for detecting the levels of interleukin-12 (IL-12), IL-13 and TNF-α by ELISA. The right lung tissues were used for pathological observation and HE staining, while the left lung tissues were used to detect the expression of NF-κB p50, I-κBα and p38 mitogen-activated protein kinase (p38 MAPK) at mRNA and protein levels. RESULTS: The results of MP nucleic acid detection showed that all the rats except blank control group were MP nucleic acid positive, indicating that the rat model of MP infection was successfully established. On the 1st day of the treatment, the pathological scores of the lung tissues in model group and Jiedu-Qingfei group were significantly higher than those in blank control group (P<0.05). After treatment, the pathological scores of the lung tissues in mo-del group were significantly higher than those in blank control group and Jiedu-Qingfei group. The levels of IL-12 in the serum and BALF in model group were significantly lower than those in blank control group after MP infection (P<0.05), while those after treatment with Jiedu-Qingfei mixture were significantly higher than those in model group (P<0.05). The levels of IL-13 and TNF-α in the serum and BALF of MP-infected rats were increased significantly, while those after treatment with Jiedu-Qingfei mixture were significantly lower than those in model group (P<0.05). The mRNA expression levels of NF-κB p50 and p38 MAPK in model group were increased significantly (P<0.01). After treatment, the mRNA expression levels of NF-κB p50 and p38 MAPK were decreased significantly compared with model group (P<0.01). The mRNA expression level of I-κBα in model group was significantly lower than that in control group. After treatment, the mRNA expression of I-κBα in Jiedu-Qingfei group was significantly higher than that in model group (P<0.05). The protein levels of NF-κB p50 and p38 MAPK in the lung tissues of model group were significantly higher than those of blank control group. After treatment, the protein expression of NF-κB p50 and p38 MAPK was decreased significantly. The protein level of I-κBα in model group was significantly lower than that in blank control group, and after treatment with Jiedu-Qingfei mixture, the protein expression level of I-κBα was increased significantly (P<0.05). CONCLUSION: Jiedu-Qingfei mixture may attenuate lung tissue inflammation caused by MP through NF-κB and p38 MAPK pathways.     

β-carotene attenuates weaning-induced apoptosis via inhibition of PERK-CHOP and IRE1-JNK/p38 MAPK signalling pathways in piglet jejunum

Weaning may cause oxidative injury, immune response impairment, apoptosis and other injuries in piglets. Oxidative and endoplasmic reticulum stress (ERS) can elicit inflammatory responses, and persistent oxidative and ERS also may lead to apoptotic cascades, which is associated with the pathogenesis of multiple diseases. β-carotene, a natural carotenoid, has potential anti-inflammatory and antioxidant functions. However, the effect of β-carotene on apoptosis in weaned piglets and the detailed molecular mechanism remain unclear. In this study, we found that β-carotene decreased malondialdehyde (MDA) levels and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in piglet serum. β-carotene could inhibit the mRNA levels of caspase-3 significantly, but had no significant inhibitory effect of the mRNA levels of caspase-9 and caspase-12 in the piglet jejunum. In addition, β-carotene decreased the activation of GRP78, CHOP, and JNK/p38 MAPK and the ratio of Bax/Bcl-2. Furthermore, β-carotene had a significant influence on the activation of ERS and apoptosis-related signals in TG-induced IPEC-J2. In the present study, β-carotene pre-treatment attenuated the ratio of Bax/Bcl-2 and prevented TG-induced increases in the level of PERK-CHOP and IRE1-JNK/p38 MAPK pathway activation in a dose-dependent manner. Overall, these findings indicate that β-carotene may protect weaning-induced apoptosis through inhibiting ERS.     

Mapping soil salinity and pH across an estuarine and alluvial plain using electromagnetic and digital elevation model data

Increasing pressures from agriculture and urbanization have resulted in drainage of many floodplains along the eastern Australian coastline, which are underlain by sulphidic sediments, to lower water tables and reduce soil salinity. This leads to oxidation of the sediments with a rapid decline in pH and an increase in salinity. Accurately mapping soil salinity and pH in coastal acid sulphate soil (CASS) landscapes is therefore important. One required map is the extent of highly acidic (i.e. pH < 4.5) areas, so that the application of alkaline amendments (e.g. lime) to neutralize the acid produced can be specifically targeted to the variation in pH. One approach is to use digital soil mapping (DSM) using ancillary information, such as an EM38, digital elevation models (DEM – elevation) and trend surface parameters (east and north). We used an EM38 in the horizontal (EM38h) and vertical (EM38v) modes together with elevation data to develop multiple linear regressions (MLR) for predicting EC_1:5 and pH. For pH, best results were achieved when the EM38 EC_a data were log‐transformed. By comparing MLR models using REML analysis, we found that using all ancillary data was optimal for mapping EC_1:5, whereas the best predictors for pH were north, log‐EM38v and elevation. Using residual maximum likelihood (REML), the final EC_1:5 and pH maps produced were consistent with previously defined soil landscape units, particularly CASS. The DSM approach used is amenable for mapping saline soils and identifying areas requiring the application of lime to manage acidic soil conditions in CASS landscape.     

Cyclooxygenase (COX) inhibitors and the intestine

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins.     

黄芪多糖在LPS诱导的DF-1细胞炎症反应中的抗炎作用及其调节机制

为探讨黄芪多糖(Astragalus polysaccharide,APS)在LPS(lipopolysaccharide,LPS)诱导的鸡胚成纤维细胞系DF-1(chicken embryonic fibroblast cell line,DF-1)炎症模型中对IL-1β和TNF-α表达的影响,以及细胞因子信号转导抑...     

All-trans retinoic acid attenuates blood-brain barrier injury induced by cerebral ischemia-reperfusion in rats through JNK/P38 MAPK signaling pathway

AIM: To investigate the effect of all-trans retinoic acid (ATRA) on blood-brain barrier after cerebral ischemia-reperfusion (CIR) injury in rats and its possible role mechanism.METHODS: Male SD rats were randomly divided into sham group, model (CIR) group and CIR+ATRA (10, 30 and 90 mg/kg) groups. The rat model of CIR injury was established by MCAO thread occlusion method. After ischemia for 1.5 h and reperfusion for 24 h, the neurological functional behavioral score, cerebral infarction volume, brain water content and Evans blue content were determined. The activity of matrix metalloprotein-9 (MMP-9) was measured by gelatin zymography. The protein levels of claudin-5, occludin, ZO-1, JNK, p-JNK, P38, p-P38 and MMP-9 in the brain tissues were determined by Western blot.RESULTS: Compared with CIR model group, ATRA at 30 mg/kg significantly improved neurological function, and decreased cerebral infarction volume, brain water content, Evans blue content and the degradation of tight junction proteins in ischemic area (P<0.01). The activity and protein expression of MMP-9 in ischemic brain tissue were decreased (P<0.01). The phosphorylation of JNK and P38 was inhibited and the protein levels of p-JNK and p-P38 were decreased (P<0.01).CONCLUSION: ATRA reduces the damage of brain tissue and the destruction of blood-brain barrier induced by CIR in rats. The protective effect may be related to inhibiting the activation of JNK/P38 MAPK signaling pathway and MMP-9.