Effect mechanism of acupuncture for anti-asthmatic airway remodeling based on TGF-β1 / Smad3 signaling pathway / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6) + "Yuji" (LU 10) for the airway remodeling in asthma rats based on the transforming growth factor-β1 (TGF-β1)/ Smad family member 3 (Smad3) signaling pathway; and explore the efficacy difference between the two acupoint combinations.@*METHODS@#Forty SPF male SD rats, aged 4 weeks, were randomly divided into a blank group (n = 10) and a modeling group (n = 30). The ovalbumin (OVA) sensitization method was used to establish asthma model in the modeling group. After successful model preparation, the rats of the modeling group were randomized into a model group, an acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) (AAF) group, and acupuncture at "Kongzui" (LU 6)+"Yuji" (LU 10) (AAK) group, with 10 rats in each one. Starting from day 15 of the experiment, 5 min after motivating, acupuncture was applied to "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6)+"Yuji" (LU 10) in the AAF group and the AAK group respectively. The intervention was delivered for 30 min each time, once daily, lasting 3 weeks consecutively. Using lung function detector, the airway resistance (RL) and dynamic compliance (Cdyn) of the lungs were detected. The histomorphology of lung tissues was detected with HE staining and Masson staining, and the mRNA and protein expression of TGF-β1 and Smad3 in lung tissues was detected with the real-time PCR and Western blot methods.@*RESULTS@#Compared with the blank group, RL was increased and Cdyn was decreased in the rats of the model group (P<0.01); and RL was reduced and Cdyn was increased in the AAF group and the AAK group when compared with those in the model group (P<0.01, P<0.05). The rats of the model group had bronchial lumen stenosis, inflammatory cell infiltration, collagen fibre hyperplasia and thickened smooth muscle in the lung tissues when compared with those in the blank group; and in comparison with the model group, all of the above morphological changes were attenuated in the AAF group and the AAK group. Besides, these morphological changes of the lung tissues were more alleviated in the AAF group when compared with those in the AAK group. In comparison with the blank group, the mRNA and protein expression of TGF-β1 and Smad3 of the lung tissues was increased in the model group (P<0.01), and it was reduced in the AAF group and the AAK group when compared with that in the model group (P<0.05, P<0.01). The mRNA expression of TGF-β1 and Smad3 was lower in the AAF group when compared with that in the AAK group (P<0.05).@*CONCLUSION@#Acupuncture at either "Feishu" (BL 13)+"Dingchuan" (EX-B 1) or "Kongzui" (LU 6)+"Yuji" (LU 10) reduces the airway remodeling in the rats with asthma, which may be related to the down-regulation of mRNA and protein expression of TGF-β1 and Smad3. The better efficacy is obtained with acupuncture at "Feishu" (BL 13)+"Dingchuan" (EX-B 1).

Mannan-Binding Lectin Inhibits Candida Albicans-Induced DC Maturation and Cytokine Secretion / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of mannan-binding lectin (MBL) on the maturation and cytokine secretion of human dendritic cells (DC) induced by Candida albicans (C. albicans).</p><p><b>METHODS</b>The plastic-adherent mononuclear cells were prepared from the blood of healthy adult volunteers. The human peripheral blood mononuclear cells-derived dendritic cells (MNC-DC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2 days in presence or absence of C. albicans at varying concentration of human MBL ranging from 1 to 20 mg/L. DC's shape and characters were observed under inverted microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The levels of TNF-α and IL-6 were detected by ELISA. FACS also was used to investigate the interaction of MBL with immature DC(imDC) and C. albicans. Western blot was used to detect C. albicans-induced IκBα phosphorylation and p65/NF-κB translocation in DC.</p><p><b>RESULTS</b>MBL at higher concentrations (10-20 mg/L) down-regulated the expression of CD83 and CD86 on the monocyte-derived dentritic cells(MoDC) induced by C. albicans, and inhibited the production of TNF-α and IL-6 induced by C. albicans. FACS showed that MBL could not only bind to C. albicans but also bind to imDCs in a Ca2+-dependent manner. Western blot showed that MBL could decrease the phosphorylation of IκBα and the nuclear translocation of p65/ NF-κB.</p><p><b>CONCLUSION</b>MBL may inhibit TNF-α and IL-6 production induced by C. albicans in DC through NF-κB signaling pathways, suggesting that MBL can play some roles in the regulation of C. albicans-induced immune response.</p>

Opioid receptors mediate enhancement of ACh-induced aorta relaxation by chronic intermittent hypobaric hypoxia / 生理学报

The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day. The rats in control group were kept in the same environment as CIHH rats except no hypoxia exposure. The relaxation of thoracic aorta rings was recorded by organ bath perfusion technique, and expression of opioid receptors was measured by Western blot. Results are shown as follows. (1) The acetylcholine (ACh)-induced endothelium-dependent relaxation of thoracic aorta in CIHH rats was increased obviously in a concentration-dependent manner compared with that in control rats (P < 0.05). (2) This enhancement of ACh-induced relaxation in CIHH rats was abolished by naloxone, a non-specific opioid receptor blocker (P < 0.05). (3) The expressions of δ, μ and κ opioid receptors in thoracic aorta of CIHH rats were up-regulated compared with those in control rats (P < 0.05). (4) The enhancement of CIHH on relaxation of thoracic aorta was reversed by glibenclamide, an ATP-sensitive potassium channel (KATP) blocker (P < 0.05). The results suggest that opioid receptors are involved in CIHH-enhanced ACh-induced vasorelaxation of thoracic aorta through KATP channel pathways.

Effect of chronic intermittent hypobaric hypoxia on contractile activity of arteries in rats / 生理学报

The present study is aimed to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on contractile activities in isolated thoracic aorta and pulmonary artery rings and the underlying mechanism in rats. Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group (CON), 14 days CIHH treatment group (CIHH14), 28 days CIHH treatment group (CIHH28) and 42 days CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 h daily for 14, 28 and 42 d, respectively. After artery rings were prepared from pulmonary artery and thoracic aorta, the contractile activity of the artery rings was recorded using organ bath technique. Results are shown as follows. (1) There were no significant differences of noradrenaline (NA)- and KCl-induced contractions in thoracic aorta and pulmonary artery rings among CIHH and CON rats. (2) Angiotensin Ⅱ (ANGⅡ)-induced contraction in thoracic aorta rings, not in pulmonary artery rings, of CIHH rats was decreased compared with that in CON rats. There was no significant difference of ANGⅡ-induced contraction in thoracic aorta rings among CIHH rats. (3) Inhibitory effect of CIHH on ANGⅡ-induced contraction in thoracic aorta rings was endothelium-independent, and was reversed by glibenclamide (Gli), an ATP-sensitive potassium channels (K(ATP)) blocker, and L-NAME, a NO synthase inhibitor, but not by indomethacin (Indo), a cyclooxygenase inhibitor. These results suggest that CIHH attenuates the contraction induced by ANGⅡ in thoracic aorta rings of rat, which is related to the opening of K(ATP) channel and the increased production of NO.

Eeffects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta of normoxic and chronic intermittent hypobaric hypoxic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms.</p><p><b>METHODS</b>Young male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly.</p><p><b>RESULTS</b>Coptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction.</p><p><b>CONCLUSION</b>Coptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP-sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane.</p>

Effects of Honeysuckle flower and Scutellaria Baicalensis Georgi on constraction and electric activity of rabbit small intestine smooth muscle / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of Honeysuckle flower (HF) and Scutellaria Baicalensis Georgi (SBG) on contraction and electric activity of small intestine smooth muscle in rabbit and the underlying mechanisms.</p><p><b>METHODS</b>Using organ bath technique to observe the effect of HF and SBG on contractive and electric activity of small intestine smooth muscle in rabbit.</p><p><b>RESULTS</b>HF and SBG significantly decreased the amplitude, frequency and area under the curve of contractive, as well as electric activity in a dose-depended manner. IC50 of the contractive amplitude was 6.30 g/L and 1.56 g/L by Logit Loglinear analysis. The inhibitive effect of HF and SBG on contractive activity could be partly decreased by beta-receptor blocker Propranolol, NO synthase inhibitor L-NAME, and K+ channel blocker Glibenclamide. Also HF and SBG inhibited acetylcholine-induced both intracellular and extracellular calcium-depended contraction significantly.</p><p><b>CONCLUSION</b>HF and SBG obviously inhibit the contractive and electric activity of small intestine smooth muscle of rabbit. The mechanisms are related to several pathways.</p>

Decreased basic activity and induced activity of ERK1/2 pathway in hippocampal CA1/CA2 region of ovariectomized rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the relationship between the spatial learning and memory and hippocampal ERK1/2 pathway activity in ovariectomized rats.</p><p><b>METHODS</b>Female SD rats were randomly divided into sham operated group (Sham group) and ovariectomized group (OVX group), and fed 4 months. Then spatial learning and memory of rats were evaluated by the Morris water maze task. Rats in each group were randomly divided into training group and untraining group before the test. Induced activity of ERK 1/2 stimulated by learning and memory was detected in the training group, and basic activity of ERK 1/2 was detected in the untraining group. The protein expression of p-ERK 1/2 and Raf kinase inhibitor protein (RKIP) were assayed by Western blotting respectively.</p><p><b>RESULTS</b>(1) During the training session the OVX rats held longer escape latenci than the sham rats did (P < 0.05). (2) The relative level of pERK1/2 protein in training rats of the both groups was higher than that in untraining rats (P < 0.05). (3) The relative level of p-ERK1/2 protein both training and untraining rats in OVX group was lower than that in sham group correspondingly (P < 0.05). (4) Compared with sham group, the relative expression of RKIP in OVX group was significantly higher (P < 0.05).</p><p><b>CONCLUSION</b>Spatial learning and memory deficits in ovariectomized rats might be correlated with the decreased basic and induced activity of ERK1/2 pathway and increased expression of RKIP in the CA1/CA2 region of hippocampus.</p>