Adult ; Asthma ; metabolism ; physiopathology ; Basic-Leucine Zipper Transcription Factors ; genetics ; physiology ; Fanconi Anemia Complementation Group Proteins ; genetics ; physiology ; Female ; Glutamate-Cysteine Ligase ; metabolism ; Humans ; Inflammation ; metabolism ; pathology ; Male ; NF-E2-Related Factor 2 ; genetics ; physiology ; RNA, Messenger ; genetics ; metabolism ; Sputum ; cytology

AIMTo investigate the effects of protein tyrosine kinase on the inflammation and airway remodeling in lung of guinea pigs with bronchial asthma.

METHODS30 adult male guinea pigs were randomly divided into 3 groups (n=3): control group (C group), asthmatic group(A group)and genistein group (B group). Asthmatic model was established by ovalbumin intraperitoneal injection and ovalbumin inhalation. The total cell and the proportion of inflammatory cell in bronchial alveolar lavage fluid(BALF), inflammatory cell infiltration and index of remodeling of bronchiole were measured, respectively. The expression of p-tyrosine in lung tissue was examined by immunohistochemistry.

RESULTSThe total cell and proportion of eosinophil in BALF of A group were significantly higher than that of C group (P < 0.01), but compared with A group, the total cell and proportion of eosinophil in BALF of B group were much lower (P < 0.01). The number of eosinophile and lymphocyte of bronchiole in A group were significantly higher than that of C group (P < 0.01), but compared with A group, the number of eosinophile and lymphocyte in bronchiole of B group were much lower (P < 0.01). Compared with A group, the remodeling of bronchiole of B group was significantly relieved (P <0.01), there was no difference between B and C group (P > 0.05). Immunohistochemistry indicated that in A group the p-tyrosine was more positively expressed at the bronchial smooth muscle, bronchial epithelium, smooth muscle of vessel and inflammatory cell, especially at smooth muscle of bronchi and vessel and inflammatory cell than that of C group (P <0.01), there was no difference between B group and C group (P > 0.05).

CONCLUSIONPTK played a key role in inflammation and bronchial remodeling in lung of guinea pigs with bronchial asthma. The Protein tyrosine kinase inhibitor genistein could prevent and inhibit the inflammation and bronchial remodeling in lung of guinea pigs with bronchial asthma.

Airway Remodeling ; physiology ; Animals ; Asthma ; physiopathology ; prevention & control ; Genistein ; pharmacology ; Guinea Pigs ; Inflammation ; prevention & control ; Male ; Ovalbumin ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; physiology ; Random Allocation

AIM To investigate the tissue distribution of exendin-4 after administration in healthy rats. METHODS Exendin-4 was radioiodinated by the Iodo-GenTMmethod. Tissue distribution of [125I]exendin-4 was investigated after sc administration of [125I]exendin-4 at 3 μg·kg-1 in rats. Both total radioactivity and trichloroacetic acid (TCA) precipitated radioactivity were used to calculate the levels of [125I]exendin-4 in rats plasma and tissue samples after sc administration. RESULTS The tissue distribution of [125I]exendin-4 after sc injection showed substantial disposition in kidneys, lungs, bladder and pancreas. The rank order of normalized tissue distribution was kidneys＞lungs＞bladder＞pancreas＞intestine＞plasma＞adrenals>jejunum＞lymph＞liver＞spleen＞heart＞marrow＞thymus＞testicles＞brain＞muscle＞adipose. CONCLUSION [125I]Exendin-4 underwent a rapid and wide distribution in the tissues throughout the whole body within the time course examined. TCA precipitated radioactivity in kidneys was the highest, however, only trace amounts of [125I]exendin-4 was detected in the brain.

Objective　To study the effects of systemic irradiation and conglutinant drug W11-a12 on the number and some functions of wound nentrophils (Neu). Methods　Wound Neu was collected from sponges which were implanted in rat's dorsum incision. The number of Neu, as well as the phagocytic function and motility of wound Neu were measured. Results　After 4,6,8 Gy systemic irradiation, the number of white blood cells and Neu in wound, as well as the phagocytic function and chemotactic motility of wound Neu, were significantly decreased at 24 h, 48 h after wounding. W11-a12 markedly increased the number of wound Neu, improved the phagocytic function and chemotactic motility of wound Neu at 24 h, 48 h after wounding despite the rats were radiated or not. Conclusion　The results indicated that the decreased number and function of wound Neu in the early stage of wound healing contributed to the impairment of repair after systemic irradiation. W11-a12 accelerated normal and irradiation-impaired wound healing partly by increasing the number of wound Neu and improving the Neu function.

Objective　To observe some biological features of bone marrow mesenchymal stem cells and explore the best conditions for isolatin g and culturing in vitro. Methods　Common cell culture techn ique, light and electron microscopy were used to study the effects of the growth , proliferation, morphology of the bone marrow mesenchymal stem cells in differe nt adherent time, concentration of serum and cell density. Results　The best culture condition in vitro for growth was 4-24 hours adherent time, 5%-10% fetal bovine serum, (4-8)×104/ml cell density. The cells were sp indle in shape and had a strong ability of proliferation. The time for cell duplication was 3 to 4 days. The cells showed the characteristics of stem cell s in electron microscope. Conclusion　The best condition for iso lation and culture of bone marrow mesemchymal stem cells was successfully establ ished and some biological features were obserred. It found a base for further in vestigation and using of mesenchymal stem cells.

OBJECTIVETo observe the effects of acupuncture at "Feishu" (BL 13) and "Lingtai" (GV 10) on distribution taxis of paclitaxel in mice with lung cancer to discuss targeted relationship between acupoints and corresponding viscera.

METHODSAccording to randomized digital table, 315 SPF-grade BALB/C female mice were divided into 7 groups: blank group (group A), model group (group B), medication group (group C), acupuncture at non-acupoint group (group D), acupuncture at Feishu group (group E), acupuncture at Lingtai group (group F) and acupuncture at Feishu and Lingtai group (group G), 45 mice in each one. Except the blank group, the remaining groups were treated with N-nitroso-tris-chloroethyl urea (NTCU) to establish the model of squamous-cell carcinoma. After model establishment, group A, group B and group C were not treated with acupuncture; group A and group B were treated with intraperitoneal injection of 0.9% sodium chlorvde solution by 6 mL/kg while group C was treated with intraperitoneal injection of paclitaxel by 6 mL/kg. The group D, group E, group F and group G were treated with acupuncture at non-acupoint, "Feishu" (BL 13), "Lingtai" (GV 10) and "Feishu" (BL 13) plus "Lingtai" (GV 10), respectively, then were intraperitoneally injected with paclitaxel by 6 mL/kg. The treatment was all given once a day for continuous 10 days. 15 min, 30 min, 1 h, 2 h, 8 h, 12 h and 24 h after the treatments, 6 mice in each group were randomly selected and sacrificed to collect samples of lung, liver, spleen, kidney and heart, etc. High performance liquid chromatography was applied to measure the concentration of paclitaxel in each organ (lung, liver, spleen, kidney and heart) at different time points.

RESULTS(1) The content of paclitaxel in lung, kidney and heart reached the peak at 2 h, then decreased significantly in group C, group D, group E, group F and group G; the content of paclitaxel in spleen showed downtrend at each time point. The content of paclitaxel in liver reached the peak at 2 h in group C and group D; the content of paclitaxel reached the peak at 8 h in group E, group F and group G. (2) The content of paclitaxel in lung in group E and group G was higher than that in group C and group D at each time point (all P < 0.01); the content of paclitaxel in lung in group F was higher than that in group C (P < 0.01) and group D (P < 0.01) only at time point of 2 h. The content of paclitaxel in lung in group G was higher than that in group F at each time point (all P < 0.05). There was no statistical difference between group G and group E (all P > 0.05).

CONCLUSIONAcupuncture at "Feishu" (BL 13) and "Lingtai" (GV 10) could influ- ence the metabolism of paclitaxel in lung-cancer mice, leading to distribution change in each organ. As a result, it could cause targeting effects, which is more significant at "Feishu" (BL 13) and "Lingtai" (GV 10).

Acupuncture Points ; Acupuncture Therapy ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacokinetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; therapy ; Mice ; Mice, Inbred BALB C ; Paclitaxel ; pharmacokinetics ; Taxus ; chemistry

AIMTo investigate the expression and relationship of gamma-glutamylcysteine synthetase (gamma-GCS) and NF-E2-related factor2 (NRR2) in lung of rat with chronic obstructive pulmonary disease (COPD)in order to elucidate the possible important role of gamma-GCS and NRF2 in pathogenesis of COPD.

METHODSThe rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposed to cigarette smoke daily. The gamma-GCS activity was measured, the expression of gamma-GCS mRNA in lung was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), the protein expressions of NRF2, gamma-GCS in lung were detected by immunohistochemical (IH) and Western blot respectively.

RESULTSThe gamma-GCS activity was higher in COPD group than that in control group. The expressions of gamma-GCS mRNA in COPD group was stronger than those in control group. ISH showed that the gamma-GCS mRNA was expressed in alveolar epithelium and bronchial smooth muscle cell in COPD. The protein expressions of NRF2, gamma-GCS were significantly higher than the control group. IH showed that NRF2, gamma-GCS proteins were expressed in alveolar and bronchial epithelium in the COPD group. There was a positive correlation between NRF2 and gamma-GCS and gamma-GCS mRNA.

CONCLUSIONNRF2 may play an important role in the mechanism of COPD oxidative stress vis up-regulation of gamma-GCS.

Animals ; Glutamate-Cysteine Ligase ; metabolism ; Lung ; metabolism ; Male ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; Pulmonary Disease, Chronic Obstructive ; metabolism ; physiopathology ; Random Allocation ; Rats ; Rats, Wistar

AIMTo investigate the influence and the mechanism of SK on the contractility of cultured cardiomyocytes of rats.

METHODSThe primary cultured single myocardial cell was treated with SK and the contraction frequency and size of cardiomyocyte were determined by a computer image analysis system. At the same time the effects of propranolol (a beta receptor antagonist), phentolamine (a alpha receptor antagonist), DSP (a tachykinin receptor antagonist) on the action of SK were investigated.

RESULTSSK increased contractive extend of the cardiomyocyte, in which a dose-response relationship of SK at 1.78 x 10(-8) - 1.78 x 10(-5) mol/L exists. But the frequency of contraction did not change, pretreatment with propranolol, phentolamine had no action on the effect of SK, but DSP markedly attenuated the effects of SK.

CONCLUSIONSK may directly enhance the contractility of single cardiomyocyte, which may be related with the tachykinin receptor.

Animals ; Animals, Newborn ; Benzylamines ; pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; drug effects ; physiology ; Neurokinin A ; pharmacology ; Phentolamine ; pharmacology ; Propranolol ; pharmacology ; Rats ; Rats, Wistar ; Receptors, Tachykinin ; antagonists & inhibitors

0.05)between the two groups.Conclu- sion The long-term outcomes of e-CHB is not markedly different compared with that of e+CHB.

OBJECTIVETo explore the effect of combination therapy of tetramethylpyrazine (TMP) with methotrexate (MTX) on collagen induced arthritis (CIA) rats.

METHODSTotally 55 male SD rats were stratified by body weight. Nine of them were randomly recruited as the normal control group. The rest 46 were immunized with type II bovine collagen (C II) for establishing rheumatoid arthritis (RA) model. Forty successfully modeled rats were randomly divided into 4 groups according to swollen toe degree, i.e., the CIA group, the TMP group, the MTX group, and the TMP plus MTX group, 10 in each group. Rats in the MTX group were administered with MTX (1. 2 mg/kg) , once per week for 4 continuous weeks. Those in the TMP group were administered with 40 mg/kg TMP, once per day for 10 continuous days, and then discontinued for 7 successive days, and continued for another 10 successive days. Rats in the TMP plus MTX group were administered with a mixture of equal dose MTX and TMP, and when MTX was discontinue, TMP was administered according to the way in the TMP group. Equal volume of saline solution was given to rats in the normal control group and the CIA group. Clinical parameters including ankle width (mediolateral diameter) and hindpaw swelling were measured at day 0, 4, 11, 18, and 26 after treatment. Rats were sacrificed 28 days after treatment, their knee joints and ankle joints were collected for pathological analyses. Serum levels of IL-1β, IL-6, and IL-17A were detected by ELISA. Changes of fibrinogen (FIB) and platelet aggregation rate (PAg) were detected.

RESULTSCompared with the normal control group, the ankle width and hindpaw swelling increased significantly (P < 0.01), contents of FIB and PAg increased obviously (P < 0.05, P < 0.01), serum levels of IL-1β, IL-6, and IL-17 increased remarkably (P <0. 01) in the CIA group. Obvious cell proliferation, inflammatory cell infiltration, hyperemia and edema of synovial tissues could be seen. Pannus formed and immerged in cartilages, resulting in necrosis. Compared with the model group, changes of ankle width and hindpaw swelling were all alleviated in each medicated group (P <0. 05, P <0. 01). Of them, the effect was superior in the MTX group to that of the TMP group and the MTX plus TMP group (P < 0.05, P < 0.01). Contents of FIB, serum levels of IL-1β and IL-6 decreased significantly in the MTX group (P < 0.05). Contents of FIB, serum levels of IL-1β and IL-6 decreased significantly in the TMP group and the MTX plus TMP group (P < 0.05). Besides, serum levels of FIB and IL-6 were obviously lower in the MTX plus TMP group than in the TMP group and the MTX group (P < 0.01). Levels of PAg and IL-17A were more significantly lowered in the TMP group than in the MTX plus TMP group and the MTX group. Pathological changes could be alleviated in each medicated group, with the optimal effect obtained in the MTX plus TMP group.

CONCLUSIONCombination of TMP with MTX could significantly ameliorate inflammatory reactions and FIB contents of CIA rats.

Animals ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Cattle ; Collagen Type II ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hemorheology ; Interleukin-17 ; Interleukin-1beta ; Interleukin-6 ; Male ; Methotrexate ; therapeutic use ; Pyrazines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane