ABSTRACT
ObjectiveToinvestigatetheprotectiveeffectandmechanismofscutelarincombinedwith paeoniflorin after permanent cerebral ischemia in rats. Methods Forty-eight adult male SD rats w ere randomly divided into four groups: sham-operation, cerebral ischemia, scutelarin+ paeoniflorin, and cyclopamine (n=12 in each group). A model of permanent middle cerebral artery occlusion w as induced by suture method. The intraperitoneal injection of cyclopamine 6 mg/kg, a specific inhibitor of sonic hedgehog (SHH) pathw ay, at 15 min before ischemia in the cyclopamine group, w hile other groups w ere intraperitoneal y injected an equal volume of saline. At 0 hour and 3 hours after ischemia, the scutel arin+paeoniflorin group and cyclopamine group w ere intraperitoneal y injected scutel arin ( 20 mg/kg ) and paeoniflorin (30 mg/kg), while other groups were intraperitonealy injected an equal volume of saline. Neurological deficit scores w ere performed at 24 hours after ischemia, and then the rats w ere decapitated. The cerebral infarct volume w as measured by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction and Western blotting w ere used respectively to detect the expression levels of SHH, Patched-1, Gli-1 mRNAs and proteins in the ischemic cortex. Results The neurological deficit scores in the cerebral ischemia group, scutel arin+paeoniflorin group, and cyclopamine group w ere 3.33 ±0.52, 1.50 ±0.55, and 3.67 ±0.52, respectively. The neurological deficit score in the scutel arin+paeoniflorin group w as significantly low er than that in the cerebral ischemia group ( P<0.05), and the neurological deficit score in the cyclopamine group w as significantly higher than that in the scutelarin+paeoniflorin group ( P<0.05). The infarct volume percentage in the cerebral ischemia group, scutelarin+paeoniflorin group, and cyclopamine group were 31.77%±1.19%, 22.94%±2.65%, and 35.53%±0.20%, respectively. The infarct volume in the scutel arin+paeoniflorin group w as significantly less than that in the cerebral ischemia group ( P<0.05), and the infarct volume in the cyclopamine group was significantly larger than that of the scutelarin+paeoniflorin group (P<0.05). The expression levels of SHH, Patched-1, Gli-1 mRNAs and proteins in the cerebral ischemia group, scutelarin+paeoniflorin group, and cyclopamine group w ere significantly higher than those in the sham -operation group (al P<0.05). The expression levels of SHH, Patched-1, Gli-1 mRNAs and proteins in the scutelarin+paeoniflorin group were significantly higher than those in the in the cerebral ischemia group (al P<0.05), and the expression levels of Gli-1 mRNA and protein in the cyclopamine group were significantly lower than those in the scutelarin+paeoniflorin group ( al P<0.05 ). Conclusions The scutel arin combined w ith paeoniflorin has certain protective effect on focal cerebral ischemia injury in rats. Its mechanism is associated w ith the activation of SHH signaling pathw ay.
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Cerebralischemiacaninducecelnecrosisincoreoftheinfarction,andapoptosisinthe ischemic penumbra. The mitogen-activated protein kinases (MAPKs) signaling pathw ays are activated after cerebral ischemia, causing programmed cel death, including apoptosis. This article review s the relationship betw een the MAPKs signaling family and neuronal apoptosis after cerebral ischemia.
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Integrins are a family of cell adhesion receptors that mediate cell-cell and cell-extracellular matrix adhesion, and interact with cytokines through a bidirectional signal transduction,thus regulating the biological behavior of pancreatic cancer cells,such as proliferation,apoptosis,invasion,and migration etc. Molecular and animal studies indicated that integrins targeted methods might benefit the early diagnosis and drug therapy of pancreatic cancer,which offered a new approach for the study of diagnosis and treatment of pancreatic cancer.
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Atherosclerosis is the important pathologic basis of coronary artery disease,cerebrovascular disease,peripheral arterial disease and other vascular diseases.Studies have shown that the atheromatous plaques occur mainly in regions of curvature,bifurcation,and branching of the artery,indicating that low flow shear stress is closely associated with the occurrence of atherosclerosis.Low flow shear stress involves in the induction of atherosclerosis through acting on mechanosensitive molecules in endothelial cell that transduce mechanical stimuli into chemical signals,activate the corresponding intracellular signaling pathways.This article reviews the relationship between low flow shear stress and atherosclerosis.
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Objective: To investigate the effect of the ERK1/2 signal-transduction pathway on differentiation of rat mesencephalic neural stem cells (NSCs) in presence of bone marrow stromal cell-conditioned medium (BMSCs-CM) in vitro. Methods: NSCs were cultured on poly-L-lysine (PLL) coated 35 nun dishes. The neurospheres adhered to the bottom 30 min later; then the culture medium of natural differentiation group was replaced by neurobasal medium containing 2% B27; the control group was replaced with BMSCS-CM; and the inhibition group was replaced with BMSCs-CM containing PD98059 (5 μmol/L). The proportions of neurons and astrocytes and their morphological difference were observed by immunocytochemistry technique 7 d later. Results: We successfully cultured NSCs from adult rat BMSCs-CM. The proportion of neurons in the natural differentiation group (15.70±10.3)% was lower than that in the control group ([51.17±10.30]%, P<0.05); the proportion of astrocytes in the natural differentiation group (66.9± 14.8)% was higher than that in the control group ([23.26 ± 5.60]%, P<0.05). The proportion of neurons in the inhibition group (39.48 ± 7.29)% was lower than that in the control group ([51.17 ± 10.30]%, P< 0.05); the proportion of astrocytes in the inhibition group (31.01 ± 8.96)% was higher than that in the control group ([23.26 ± 5.60]%, P<0.01). Conclusion: BMSCs-CM can up-regulate the proportion of neurons in cultured NSCs and down-regulate the proportion of astrocytes, which might be mediated by the ERK1/2 signal-transduction pathway.
ABSTRACT
Objective:To investigate the effect of the ERK1/2 signal-transduction pathway on differentiation of rat mesencephalic neural stem cells(NSCs)in presence of bone marrow stromal cell-conditioned medium(BMSCs-CM)in vitro.Methods:NSCs were cultured on poly-L-lysine(PLL)coated 35 mm dishes.The neurospheres adhered to the bottom 30 min later;then the culture medium of natural differentiation group was replaced by neurobasal medium containing 2% B27;the control group was replaced with BMSCs- CM;and the inhibition group was replaced with BMSCs-CM containing PD98059(5?mol/L).The proportions of neurons and astrocytes and their morphological difference were observed by immunocytochemistry technique 7 d later.Results:We successfully cultured NSCs from adult rat BMSCs-CM.The proportion of neurons in the natural differentiation group(15.70?10.3)% was lower than that in the control group([51.17?10.30]%,P