Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats.

OBJECTIVE: Propofol is one of the most commonly used intravenous drugs to induce and maintain general anesthesia. In vivo and in vitro studies have shown that propofol can affect neuronal growth, leading to apoptosis and impairing cognitive function. The Abelson nonreceptor tyrosine kinase (c-Abl) is associated with both neuritic plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease and other neurodegenerative diseases. This study aimed to explore the effect of propofol on apoptosis and neurocognition through its regulation of c-Abl expression in vivo and in vitro. MATERIALS AND METHODS: In this study, primary hippocampal neurons were cultured and exposed to propofol at different concentrations. Protein expression was measured by Western blotting and coimmunoprecipitation. The c-Abl transcription level was verified by fluorescence quantitative PCR. Reactive oxygen species (ROS) levels were detected by flow cytometry. In addition, an animal experiment was conducted to assess neuronal apoptosis by immunofluorescence staining for caspase-3 and to evaluate behavioral changes by the Morris water maze (MWM) test. RESULTS: The in vitro experiment showed that propofol significantly decreased c-Abl expression and ROS levels. In addition, propofol has no cytotoxic effect and does not affect cell activity. Moreover, in the animal experiment, intraperitoneal injection of 50 mg/kg propofol for 5 days obviously decreased the expression of c-Abl in the neonatal rat brain (p < .05) but did not significantly increase the number of caspase-3-positive cells. Propofol treatment did not significantly reduce the number of platform crossings (p > .05) or prolong the escape latency of neonatal rats (p > .05) in the MWM test. CONCLUSIONS: The present data suggest that reduced expression of this nonreceptor tyrosine kinase through consecutive daily administration of propofol did not impair learning or memory function in neonatal rats.

Propofol postconditioning protects H9c2 cells from hypoxia/reoxygenation injury by inducing autophagy via the SAPK/JNK pathway.

Propofol postconditioning (P­PostC) offers cardioprotection in mice, and the upregulation of autophagy protects cardiac cells against ischemia/reperfusion injury. The present study aimed to examine the effects of P­PostC on the induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R) injury. Rat heart­derived H9c2 cells were exposed to H/R, comprising 6 h of hypoxia followed by 4 h of reoxygenation, as well as postconditioning with various concentrations of propofol at the onset of reperfusion. Lactate dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in myocytes subjected to H/R injury and P­PostC was detected by western blotting and immunofluorescence. Furthermore, the activation of c­Jun N­terminal kinase (JNK) in cells treated with P­PostC with or without co­treatment with SP600125, an inhibitor of JNK, was also determined by western blotting. P­PostC reduced the activity of LDH in the culture medium and the percentage of apoptotic cells compared with cells in the untreated H/R group. In addition, P­PostC induced autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The inhibition of autophagy by 3­methyladenine treatment diminished the cardioprotective effects of P­PostC. These results indicated that propofol postconditioning promoted cell survival through the induction of autophagy in H9c2 cardiac cells, and that the stress­activated protein kinase/JNK survival pathway may be partly involved in P­PostC­induced autophagy.

Synthesis and fungicidal activities of novel indene-substituted oxime ether strobilurins.

Nineteen novel indene-substituted oxime ether strobilurins, which used an indene group to stabilize the ( E)-styryl group in SYP-Z071 (an unsaturated oxime strobilurin fungicide under development by the Shenyang Research Institute of Chemical Industry), were designed and synthesized. The biological assay results showed that all compounds possessed good or excellent fungicidal activities. It was found that most of the compounds showed higher fungicidal activities against Pyricularia oryzae, Phytophthora infestans, Erysiphe graminis, and Colletotrichum lagenarium than SYP-Z071 at the tested concentration. The biological assay results also indicated that most of the compounds exhibited higher in vivo fungicidal activities against cucumber Pseudoperonospora cubensis and C. lagenarium than the commercial fungicides trifloxystrobin and kresoxim-methyl at a concentration of 6.25 mg/L. Furthermore, it was found that alpha-(methoxyimino)- N-methylphenylacetamide oxime ethers 6m- s exhibited a broad spectrum and remarkably higher activities against all tested fungi. Especially, the 6-methylindene-substituted compound 6p was identified as the most promising candidate for further study.

[Studies of potassium channel in pulmonary artery smooth muscle cells derived from renal hypertensive rat].

AIM: To investigate the differences of membrane capacitance, membrane current, current density and I-V curves between smooth muscle cells isolated from RHR and NTR pulmonary arteries. METHODS: Under antiseptic conditions, the left renal artery was exposed through a retroperitoneal flank incision and carefully dissected free of the left renal vein. A silver clip with an internal diameter of 0.2-0.3 mm was placed around the left renal artery, resulting in partial occlusion of renal perfusion. SBP was observed by tail blood pressure. Whole cell recordings were made from smooth muscle cells freshly isolated from pulmonary arteries derived from RHR or NTR. RESULTS: The average membrane capacitance was (3.43 +/- 1.16) pF, decreased by 31.1%; membrane current was (0.54 +/- 0.26) nA, decreased by 68.2%; current density was (180 +/- 90) pA/pF, decreased by 48.6%; membrane potential was (-26.96 +/- 7.23) mV, decreased by 2.5%, all compared with that of NTR respectively. Iptakalim hydrochloride at the concentration of 0.1-100 micromol/L can significantly increased NTR potassium currents. Iptakalim hydrochloride 1-100 micromol/L can significantly increased RHR potassium currents. CONCLUSION: Membrane capacitance, membrane current, membrane potential were decreased, I-V curves were shift downward, compared with that of NTR. Iptakalim hydrochloride might significantly increase NTR and RHR potassium currents.

[Expression and significance of enkephalin and dopamine in experimental rat cerebral concussion tissue].

AIM: To explore the expression and significance of enkephalin and dopamine in rat cerebral concussion tissue. METHODS: 80 Wistar male rats were used to make animal model of cerebral concussion, which were sacrificed on 1,3,7,14 and 30 days after postconcussion and the brain tissues were taken out. The expression patterns of enkephalin and dopamine were studied in the course of cerebral concussion by immunohistochemical staining. RESULTS: The clinical manifestation with typical cerebral concussion character was seen in rat group with 100 g body weight. The mainly pathologic changes were cerebral vascular constriction and dilatation, congestion and edema of cerebral tissue, and neuronal degeneration and necrosis. Expression of enkephalin was increased on day 1 after injury and the enkephalin positive area was in the plasma of endothelial cells in cerebral cortex, hippocamp and cerebellum. The expression of enkephalin reached the peak on day 7 after injury, and the positive area was also seen in the plasma of neurons in cerebral cortex, hippocamp and cerebellum. From 14 days after injury, the expression of enkephalin decreased gradually, but until 30 days after injury it was still higher than that of controls. Expression of dopamine increased in 7 days after injury and the positive area was seen in the plasma of endothelial cells and in the vessel wall in cerebral cortex, hippocamp, thalamus and cerebellum, and had no notable changes at other time points. CONCLUSION: The mainly pathologic changes after cerebral concussion were blood circulatory disorder and denaturation and necrosis of parenchymal cells. Enkephalin and dopamine may participate in the pathophysiological course of cerebral injury after cerebral concussion, and play an important role in the blood vessel injury, regulation of blood-brain barrier and the denaturation and necrosis of nerve cells.