OBJECTIVETo observe the effect of calcitonin gene-related peptide (CGRP) on pulmonary vascular collagen accumulation in hypoxia rats in order to study the effect of CGRP on hypoxic pulmonary vascular structural remodeling and its possible mechanism.

METHODSRats were acclimated for 1 week, and then were randomly divided into three groups: normoxia group, hypoxia group, and hypoxia plus capsaicin group. Pulmonary arterial hypertension was induced by hypoxia in rats. Hypoxia plus capsaicin group, rats were given capsaicin (50 mg/(kg x d), s.c) 4 days before hypoxia to deplete endogenous CGRP. Hypoxia (3% O2) stimulated proliferation of pulmonary arterial smooth muscle cells (PASMCs) and proliferation was measured by BrdU marking. The expression levels of CGRP, phosphorylated ERK1/2 (p-ERK1/ 2), collagen I and collagen III were detected by real-time PCR or Western blot.

RESULTSRight ventricle systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) of pulmonary arterial hypertension (PAH) rats induced by hypoxia were higher than those of normoxia rats. By HE and Masson staining, it was demonstrated that hypoxia also significantly induced hypertrophy of pulmonary arteries and increased level of collagen accumulation. Hypoxia dramatically decreased the CGRP level and increased the expression of p-ERK1/2, collagen I, collagen III in pulmonary arteries. All these effects of hypoxia were further aggravated by pre-treatment of rats with capsaicin. CGRP concentration-dependently inhibited hypoxia-induced proliferation of PASMCs, markedly decreased the expression of p-ERK1/2, collagen I and collagen III. All these effects of CGRP were abolished in the presence of CGRP8-37.

CONCLUSIONThese results suggest that CGRP might inhibit hypoxia-induced PAH and pulmonary vascular remodeling, through inhibiting phosphorylation of ERK1/2 and alleviating the collagen accumulation of pulmonary arteries.

Animals ; Calcitonin Gene-Related Peptide ; pharmacology ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Familial Primary Pulmonary Hypertension ; Hypertension, Pulmonary ; etiology ; metabolism ; Hypoxia ; complications ; MAP Kinase Signaling System ; Male ; Phosphorylation ; Pulmonary Artery ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of an anti-fibrotic tetra peptide Ac-SDKP on vascular fibrosis by regulating extracellular regulated protein kinase (ERK1/2) activity through Ang II.

METHODSRat vascular adventitial fibroblasts were cultured in vitro. They were randomly divided into control group, Ang II (10(-6) mmol/L) group, Ang II and Ac-SDKP joint action group, PD98059 group. Type I, III collagen contents in adventitia fibroblasts were measured by RT-PCR and the expressions of matrix metalloproteinases (MMP-2) and transforming growth factor-beta1 (TGF-beta1) were determined by Western blot.

RESULTSAc-SDKP could reduced Ang II-induced expression of type I, III collagen secretion and TGF-beta1 at mRNA,and increase MMP-2 expression, PD98059 could inhibit the above effect.

CONCLUSIONThe results suggested that Ac-SDKP could inhibit the formation and development of vascular fibrosis through blocking ERK1/2 pathway mediated by Ang II. Ac-SDKP therefore served as an antifibrotic factor in vascular fibrosis.

Angiotensin II ; adverse effects ; Animals ; Cells, Cultured ; Collagen Type I ; biosynthesis ; Collagen Type III ; biosynthesis ; Fibroblasts ; cytology ; drug effects ; metabolism ; Flavonoids ; pharmacology ; MAP Kinase Signaling System ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Oligopeptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

Animals ; Codonopsis ; Drugs, Chinese Herbal ; pharmacology ; Fatigue ; Male ; Mitochondria, Heart ; drug effects ; metabolism ; Oxidative Stress ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Selenium

OBJECTIVETo observe the change of erythrocyte theology in rabbits with acute renal failure (ARF).

METHODSThirty-eight healthy rabbits were randomly divided into control group (n = 8), model group (establishing ARF model via intramuscular injection 1% HgCl2, and divided into 12 h, 24 h, 48 h subgroups, all n = 10), the arterial blood sample was taken out through carotid artery at corresponding times after anesthetization with urethane, for detecting the indices of renal function and erythrocyte rheology.

RESULTSThe levels of urea and creatinine in plasma of model rabbits at 12 h, 24 h and 48 h were higher than those of control group, and there was a rise trend along with the time extension. The erythrocytes electrophoresis time at 12 h of model group was higher, the electrophoresis rate and migration rate of erythrocytes were lower compared with those of control group; the erythrocytes electrophoresis time at 24 h of model group was lower and the electrophoresis rate and migration rate were higher compared with those of model group at 12 h; and there were no statistical differences in erythrocytes electrophoresis indices between model group at 48 h and other groups. Meanwhile, there was a rise trend in erythrocyte sedimentation rate (ESR), K value of equation and emendation along with the time extension of ARF, but these indices only at 48 h of model group was lower significantly than that of control group. There were no statistical differences in aggregation index and deformability index of erythrocytes among groups.

CONCLUSIONDuring the process of ARF, the erythrocytes electrophoresis time lengthen and electrophoresis rate and migration rate decrease at early stage, and these indices gradually return to normal; the indices of ESR increase gradually.

Acute Kidney Injury ; blood ; physiopathology ; Animals ; Erythrocyte Indices ; Erythrocytes ; physiology ; Hemorheology ; Rabbits

OBJECTIVETo observe the dynamic changes of proliferation and differentiation of neural stem cells (NSCs) in subventricular zone (SVZ) and dentate gyrus (DG) in vascular dementia (VD) rats.

METHODSVD models were established by repeatedly clipping the common carotid arteries of the rat in combination with an intraperitoneal injection of sodium nitroprusside solution in anesthetized SD rats. Morris maze test was used to detect the learning and memory ability of the rats and immune fluorescence single and double labeling method to detect the proliferation and differentiation of neural stem cells and the expression of neurogranin (Ng) at 15 d, 1 month, 2 month, 4 month time points.

RESULTSCompared with sham-operated group, the escape latency of model group rats were significantly longer at all the time points (P < 0.01). The BrdU positive cells in SVZ and DG of VD model groups were markedly increased in comparison with sham-operated group at 15 d and 1 month time point (P < 0.01), and the number of BrdU positive cells in SVZ of model groups were still larger than that of sham-operated group at 2 month and 4 month time point (P < 0.01). In model group, the number of the BrdU/Ng double staining cells were increased and higher than that in sham-operated groups (P < 0.05).

CONCLUSIONThe proliferation of NSCs can be enhanced noticeably in a certain time in SVZ and DG region and NSCs differentiate into mature neurons with the expression of Ng in DG region in VD rats, which may play some compensatory roles in the nerve regeneration and functional repairmen after cerebral injury of VD.

Animals ; Cell Differentiation ; Cell Proliferation ; Dementia, Vascular ; Dentate Gyrus ; cytology ; Ependyma ; cytology ; Male ; Maze Learning ; Nerve Regeneration ; Neural Stem Cells ; cytology ; Rats ; Rats, Sprague-Dawley

Apoptosis ; Colonic Neoplasms ; metabolism ; pathology ; HT29 Cells ; Humans ; Insulin-Like Growth Factor Binding Proteins ; metabolism

Animals ; Drugs, Chinese Herbal ; pharmacology ; Male ; Myocytes, Cardiac ; drug effects ; enzymology ; Physical Conditioning, Animal ; Rats ; Rats, Wistar

OBJECTIVETo observe the influences of quercetin (Que) on the contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism.

METHODSWith the isothermal perfusion of small intestine in vitro. The influences of quercetin on the spontaneous contraction of small intestine and contraction induced by Ach, histamine and Bacl2 were observed and the mechanism of quercetin was studied.

RESULTSQuercetin reduced the tension of contraction of small intestine smooth muscle in rabbits in a dose-depended manner. Quercetin could completely block the contraction of Bay K8644. Heparin could also block the inhibition of quercetin on small intestine smooth muscle but ruthenium red (RR) had no effect on the relaxation of quercetin. Nitro-L-arginine methylester(L-NAME) inhibited the relaxation of quercetin.

CONCLUSIONQuercetin inhibits the contraction of small intestine smooth muscle of rabbits in vitro. The mechanism may be related to increase NO concentration in small intestine smooth muscle so that it inhibits extracellular Ca2+ inflowing via cell membrane. And quercetin has effect on intracellular Ca2+ releasing via IP3 of sarcoplasmic reticulum.

Animals ; Calcium ; metabolism ; In Vitro Techniques ; Intestine, Small ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Quercetin ; pharmacology ; Rabbits ; Sarcoplasmic Reticulum ; drug effects ; metabolism

OBJECTIVETo explore the relationship between nitric oxide (NO) in central nervous system and exercise-induced fatigue stress and to study the effect of L-arginine (L-Arg), as a substrate of nitric oxide, on the exercise capacity and NO content in the exhausted rat brain and blood.

METHODSThrough an implanted cannula, the normal saline or L-Arg was microinjected into rat's intracerebroventrical for consecutive four days. Then an acute exhaustive model (on the speed of 18 m/min, an inclination of 5 degrees) was established with animal treadmill. The time of exercise till exhaustion was recorded, and the total workload was calculated that represented the exercise capacity. Nitrate and nitrite (NO3/NO2-, NOx-) levels in blood, hypothalamus and hippocampus were assayed.

RESULTSBoth the time of exercise till exhaustion and total workload in the LArg group increased respectively by 51.8% and 50.08% (P < 0.05), compared with those in the control. The NOx- content in hypothalamus in the L-Arg group (8.93 +/- 1.83) micromol/g pro was larger than that in the control (4.25 +/- 0.79) micromol/g pro, (P < 0.01). There was no significant difference in NOx- content in brain and hippocampus between the two groups. The total workload was positively correlated with NOx- concentration in hypothalamus (P < 0.01). However, there was no correlation between workload and changes in hippocampus NOx- content at fatigue.

CONCLUSIONIntracerebroventricular microinjection of L-Arg may enhance the exercise capacity and lead to up-regulation of NO by means of L-Arg-NO signal path in the hypothalamus. Hypothalamus may be a key site in brain in the modulation of physiological exercise.

Animals ; Arginine ; administration & dosage ; pharmacology ; Hippocampus ; metabolism ; Hypothalamus ; metabolism ; Lateral Ventricles ; Male ; Nitric Oxide ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of lipopolysaccharide (LPS) on airway inflammation, airway remodeling and the expression of Toll-like receptor 4 (TLR4) mRNA in asthmatic rats.

METHODSTwenty-four SPF level SD rats were randomly divided into four groups (n = 6): control group, low dose of LPS group, high dose of LPS group and asthma group. Using ovalbumin (OVA) to sensitize and challenge to establish asthmatic rat model. Observed pathological changes of lung tissue by HE staining, inflammatory cell infiltration was observed by airway wall eosinophils (EOS) counts; airway resistance was determined; image analysis software was used to determine the thickness of airway wall, detected airway smooth muscle TLR4 expression levels by RT-PCR.

RESULTSThe rat airway resistance and the EOS number of airway wall and the thickness of airway wall in asthma group, low dose of LPS group and high dose of LPS group were significantly higher than those in control group (P < 0.01). The above-mentioned parameters of high dose of LPS group showed significantly lower than those in asthma group and low dose of LPS group (P < 0.05). The expression of rat airway smooth muscle TLR4 mRNA in low dose of LPS group and high dose of LPS group were significantly higher than those in asthma group (P < 0.01). And the expression of rat airway smooth muscle TLR4 mRNA in high dose of LPS group was significantly higher than that in low dose of LPS group (P < 0.05).

CONCLUSIONTLR4 plays an important role in asthmatic airway inflammation and airway remodeling, LPS may play double-sided regulation in asthmatic airway inflammation and airway remodeling by activated TLR4.

Airway Remodeling ; drug effects ; Animals ; Asthma ; metabolism ; pathology ; physiopathology ; Inflammation ; metabolism ; Lipopolysaccharides ; adverse effects ; pharmacology ; Lung ; metabolism ; physiopathology ; Male ; Muscle, Smooth ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism