Zhongguo yao li xue bao = Acta pharmacologica Sinica最新文献

Aim: To study the effects of lipopolysaccharides (LPS) and pre-inflammatory cytokines on nitric oxide (NO) production from cultured astrocytes.

Methods: Nitrites in supernatants were measured with Griess assay.

Results: The NO production from cultured human BT325 astrocytoma cells started when cultured for 4 h, reached the peak concentration (15.0 mumol.L-1) at 12 h, maintained a high level (15.0-17.5 mumol.L-1) up to 72 h, and was enhanced by LPS 1 mg.L-1, interferon-gamma (IFN-gamma) 100 kU.L-1, tumor necrosis factor-alpha (TNF-alpha) 100 kU.L-1, interleukin (IL)-1 100 kU.L-1, or IL-2 100 kU.L-1. The enhancements of TNF-alpha, IL-1, IL-2, or the mixture of the above four cytokines were higher.

Conclusion: Stimulants and pre-inflammatory cytokines enhance astrocytes producing NO.

Aim: To study the role of dopamine (DA) receptors in l-tetrahydropalmatine (l-THP)-induced antinociception.

Methods: The intraperitoneal (i.p.) and intrathecal (ith) injections were used to give the drugs. The tail-flick test was used to assess the nociceptive threshold of rats.

Results: By i.p. injection, l-THP (10, 20, 40 mg.kg-1) as well as D2 receptor antagonist spiperone (1, 2, 3 mg.kg-1) produced dose-dependent antinociceptive effects on the nociception of rats, while D2 receptor agonist quinpirole, D1 receptor agonist SKF38393, and D1 receptor antagonist Sch-23390 showed no antinociception. Moreover, l-THP- or spiperone-induced antinociception was markedly attenuated by quinpirole (2, 3 mg.kg-1) but not SKF38393 or naloxone. On the other hand, ith quinpirole (20, 30, 40 micrograms.kg-1) also induced a dose-dependent antinociception, while ith l-THP, spiperone, SKF38393, and Sch-23390 did not exhibit any antinociception. Furthermore, ith spiperone (20, 30, 40 micrograms.kg-1) but not Sch-23390 dose-dependently antagonised the antinociception induced by quinpirole. l-THP (ith, 100, 200, 300 micrograms.kg-1) also dramatically attenuated the quinpirole-induced antinociception with a dose-dependent relationship.

Conclusion: Activating the spinal D2 receptor or blocking the supraspinal D2 receptor produces antinociception. D1 receptor might be not directly involved in the antinociception. l-THP (as a D2 antagonist) as well as spiperone produces antinociception via blocking the supraspinal D2 receptor.

Aim: To study the potential roles of protein kinase C (PKC) on expression of intercellular adhesion molecule-1 (ICAM-1) in rat brain microvascular endothelial cells (RBMEC).

Methods: ICAM-1 expression in RBMEC was measured by ELISA analyses.

Results: Phorbol ester (PMA) enhanced the expression of ICAM-1 in a concentration (10-100 nmol.L-1) and time (4-16 h)-dependent manner in RBMEC. Pentoxifylline (PTX) 1-100 mumol.L-1 and the PKC inhibitor H7 5-50 mumol.L-1 prevented PMA-induced stimulation of ICAM-1 expression. At PTX 100 mumol.L-1 and H7 50 mumol.L-1, they reached maximal inhibitory effects [ICAM-1 expression (A) from (0.410 +/- 0.014) to (0.175 +/- 0.022) and (0.182 +/- 0.013), respectively; P < 0.01].

Conclusion: Activation of PKC in RBMEC is associated with increased expression of ICAM-1 in RBMEC. PTX and H7 preincubation may inhibit PKC-induced up-regulation of ICAM-1.

Aim: To study the blood schizontocidal effect of oral artesunate on P berghei in mice and P knowlesi in monkey.

Methods: Effects of artesunate and chloroquine were detected with "4-day test" and "28-day test" on P berghei in mice and "7-day test" on P knowlesi in Macaca mudatta.

Results: The suppressive efficacy of oral artesunate was inferior to chloroquine on P berghei K173 strain but the time for 50% and 90% reduction and the time of clearance of parasitemia was 10-15 h shorter than that of chloroquine. Its curative effect on RC/K173 line was markedly superior to that of chloroquine. Moreover, artesunate showed no cross-resistance with chloroquine, index of resistance I90 was only 1.4. At 31.6, 10.0, and 3.16 mg.kg-1, artesunate and chloroquine oral administrations cured P knowlesi in all monkeys. Recrudescence did not occur in 105 d.

Conclusion: The study of effects of oral artesunate in P berghei/mice and P knowlesi/Macaca mulatta model provided a useful index for clinical trial.

Aim: To study the protective effect of dl-3-n-butylphthalide (NBP) on blood-brain barrier (BBB) damage induced by reperfusion following focal cerebral ischemia.

Methods: Focal cerebral ischemia in rats was performed by inserting a nylon suture into intracranial segment of internal carotid artery to block the origin of middle cerebral artery and reperfusion by withdrawing the nylon suture. Permeability of BBB was determined by extravasation of the protein-bound Evans blue dye to cerebral cortex and further evaluated by immunohistochemical or electronmicroscopic method.

Results: Reperfusion for 3 h following focal cerebral ischemia for 3 h produced BBB damage which exhibited the increase in extravasation in cerebral cortex, elevation of the expression of immunoglobulin (IgG), and pore formation in endothelial cell membrane of capillary in cerebral cortex. NBP (5-20 mg.kg-1) decreased the extravasation in a dose-dependent manner. The expression of IgG in cerebral cortex was decreased and the ultrastructure damage of capillaries was alleviated after treatment with NBP. NBP 20 mg.kg-1 also alleviated brain edema caused by 3-h reperfusion following 3-h middle cerebral artery occlusion (MCAO).

Conclusion: NBP has protective effect on BBB damage induced by reperfusion after MCAO.

Aim: To study the effects of berbamine (Ber) on [Ca2+]i homeostasis induced by adenosine triphosphate (ATP) in vascular smooth muscle cells (VSMC) of rabbits and cardiomyocytes of rats.

Methods: Both cell types were cultured and loaded with Fura 3-AM. [Ca2+]i was measured by fluorescent intensity (FI) in each cell with confocal microscopy.

Results: (1) ATP 30 mumol.L-1 elevated [Ca2+]i in VSMC and cardiomyocytes, FI values reached 660 +/- 258 and 1058 +/- 252 from 250 +/- 84 and 218 +/- 76 at 19 s +/- 5 s and 11.8 s +/- 2.4 s, but FI in nucleus was not changed in VSMC. (2) Ber 30 mumol.L-1 did not affect the resting FI in both cell types, but prolonged the time to peak (P < 0.01) and reduced the FI elevated by ATP (P < 0.01), but not completely inhibited even at 100 mumol.L-1. (3) In D-Hanks' solution or in the presence of egtazic acid (EGTA) 3 mmol.L-1, the inhibitory effect of Ber was not seen (P > 0.05). (4) All effects of Ber on ATP-induced [Ca2+]i mobilization were similar to those of Ver 10 mumol.L-1.

Conclusion: In VSMC and cardiomyocytes, ATP-induced CA2+ influx was inhibited by Ber and Ver, while the Ca2+ release was not.

Aim: To study the antiviral effects of rhIFN-alpha 1 (Chinese silkworm gene recombinant interferon alpha 1) on 7 influenza viruses in MDCK cells and in mouse pneumonia caused by PR8 virus.

Methods: 100TCID50 virus (H1N1, H2N2, H3N3, type B, type C, clinical A1, and clinical B) were inoculated into MDCK cells, PR8 viruses were dropped nasally in mice, the antiviral effects of rhIFN-alpha 1 were observed.

Results: The minimal effective concentrations of rhIFN-alpha 1 against these 7 influenza viruses were 12.5, 25, 50, 25, 12.5, 25, and 12.5 kU.L-1, respectively. The infectious therapeutic indices of rhIFN-alpha 1 to these viruses in MDCK cells were 8 x 10(3), 4 x 10(3), 2 x 10(3), 4 x 10(3), 8 x 10(3), 4 x 10(3), and 8 x 10(3), respectively. The inhibitory indices of rhIFN-alpha 1 to the 7 influenza viruses in MDCK cells were 3.6, 4.7, 3.5, 3.3, 3.9, 4.6, and 3.5, respectively. The rhIFN-alpha 1 inhibited the intracellular replication of influenza viruses effectively, but did not kill viruses directly. The rhIFN-alpha 1 prolonged the life span of mice infected with pneumonia by influenza virus A strain PR8 to 94.2%-132.7%. It inhibited the inflammation and hyperplasia of interstitial fibers, and decreased the virus titer. The inhibitory rates of rhIFN-alpha 1 to pulmonary-indice were 14.8%-37.4%.

Conclusion: rhIFN-alpha 1 inhibited the proliferation of influenza virus and improved the symptom of mouse pneumonia caused by influenza virus.

Aim: To observe the effects of different subtypes of central nicotinic receptor on learning and memory.

Methods: Passive avoidance response, including step-down avoidance and step-through avoidance in mice and long-term potentiation (LTP) in rat hippocampal slices.

Results: Hexamethonium (C6) 7 micrograms/mouse and kappa-bungarotoxin (kappa-BTX) 0.6 microgram/mouse inhibited the acquisition of avoidance conditioning in mice, and kappa-BTX yielded this effect with a dose-response relationship. kappa-BTX 1 mumol.L-1 suppressed the induction of LTP (P < 0.05), but not normal synaptic transmission and maintenance of LTP in rat hippocampal slices.

Conclusion: The subtypes of central nicotinic receptor sensitive to kappa-BTX play an important role in learning and memory.

Aim: To study the curative effects of recombinant human basic fibroblast growth factor (rh-bFGF) on gastric ulcer healing.

Methods: Pylorus ligated, water immersion stress-induced, reserpine-induced, and acetic acid-induced gastric ulcers in rats or mice were prepared. Morphometric analyses on ulcer were performed using microscope and true color image analysis system. The DNA and RNA contents were measured by diphenylamine method and orcinol method, respectively.

Results: In acetic acid-induced gastric ulcers in rats, rh-bFGF 2.5-40 kU.kg-1 i.g. accelerated the chronic ulcer healing with a bell-shaped dose-effect curve and the best dosage was 10 kU.kg-1. The regenerated gland epithelium width, density of capillaries in granulation tissue, and collagen content in scar tissues obviously increased in rh-bFGF-treated groups. Simultaneously, rh-bFGF promoted the differentiation and maturation of regenerated glands around ulcers. rh-bFGF 2-4 kU.kg-1 s.c. also increased the synthesis of RNA in ulcer tissues. In acute gastric ulcers, rh-bFGF i.g. was only effective on pylorus ligated ulcers, but showed no effect on total acid output and pepsin activity in gastric juice of rats.

Conclusion: rh-bFGF promoted the gastric ulcer healing and improved the quality of gastric ulcer healing.

Aim: To evaluate the effects of L-pyroglutamic acid (L-PGA, L-5-oxo-2-pyrrolidinecaroxylic acid) on sodium glutamate-induced neurotoxicity in rat cortical neurons.

Methods: In primary cortical cultures from 16-d-old fetal rat, neuronal viability and contents of nitrite in the bathing medium after transient exposure to sodium glutamate (Glu) were measured; with Fura 2-AM as an intracellular calcium indicator, AR-CM-MIC cation measurement system was used to examine cytosolic free calcium ([Ca2+]i).

Results: L-PGA 10-80 mumol.L-1, inhibited Glu (500 mumol.L-1)-induced neuronal loss in a concentration-dependent manner with IC50 value of (41 +/- 9) mumol.L-1 (95% confidence limits: 30.3-54.7 mumol.L-1). L-PGA also attenuated Glu-induced NO release. L-PGA 1, 3, 10, 30, and 100 mumol.L-1 depressed Glu-caused [Ca2+]i elevation by 20.5%, 34.4%, 47.7%, 70.6%, and 80.4%, respectively.

Conclusion: L-PGA protects cortical neurons against Glu-induced neurotoxity which may be related to inhibition of NO formation or suppression of the rise in [Ca2+]i.