RESUMO
OBJECTIVE To investigate the impacts of isorhynchophylline （IRN） on airway inflammation in asthmatic mice by regulating the monocyte chemotactic protein-1 （MCP-1）/CC chemokine receptor 2 （CCR2） signaling pathway. METHODS The asthmatic mice model was established by injecting and inhaling ovalbumin. The successfully modeled mice were randomly grouped into asthma group， IRN low-dose group （IRN-L， intragastric administration of 10 mg/kg IRN）， IRN high-dose group （IRN-H， intragastric administration of 20 mg/kg IRN）， IRN-H+CCL2 group [intragastric administration of 20 mg/kg IRN+intraperitoneal injection of 7.5 ng CC chemokine ligand 2 （CCL2）] and positive control group （intraperitoneal injection of 2 mg/kg dexamethasone）. The mice injected and inhaled with sterile phosphate-buffered solution were included in the blank control group， with 10 mice in each group. The mice in administration groups were given relevant medicine once a day， for consecutive 2 weeks. The levels of airway hyperreactivity indexes such as enhanced （Penh） value， tumor necrosis factor-α （TNF-α），interleukin-13 （IL-13） and IL-4 in serum， the number of eosinophil （EOS）， lymphocyte （LYM） and neutrophils （NEU） in alveolar lavage fluid and the protein expressions of MCP-1 and CCR2 in lung tissue were observed in each group； the pulmonary histopathological changes were observed， and inflammatory cell infiltration score was evaluated. RESULTS Compared with the blank control group， the infiltration of inflammatory cells in the lung tissue of mice was more significant in the asthma group， and there was swelling and shedding of cells； inflammatory infiltration score， Penh value， the levels of IL-4， IL-13 and TNF-α， the number of EOS， NEU and LYM， the protein expressions of MCP-1 and CCR2 were increased significantly （P＜0.05）. Compared with the asthma group， the pathological injuries of the IRN-L group， IRN-H group and positive control group were improved， and the above quantitative indexes were decreased significantly （P＜0.05）. Compared with the IRN-L group， the above quantitative indexes of the IRN-H group and positive control group were decreased significantly （P＜0.05）. There was no statistical significance in the above quantitative indexes between the IRN-H group and the positive control group （P＞0.05）. Compared with the IRN-H group， the above quantitative indexes of the IRN-H+CCL2 group were increased significantly （P＜0.05）. CCL2 reversed the protective effect of high-dose IRN on asthmatic mice. CONCLUSIONS IRN may reduce the release of airway inflammatory factors in asthmatic mice by inhibiting the activation of the MCP-1/CCR2 signaling pathway， so as to achieve the purpose of improving asthma.
RESUMO
OBJECTIVE To study the tocolysis effects of Angelica sinensis polysaccharides on threatened abortion model rats and their impacts on Th1/Th2 balance by regulating the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway. METHODS Pregnant rats were randomly grouped into the control group， model group， A. sinensis polysaccharide group （200 mg/kg）， PI3K/AKT signaling pathway inhibitor LY294002 group （5 mg/kg）， and A. sinensis polysaccharide+LY294002 group （200 mg/kg A. sinensis polysaccharide+5 mg/kg LY294002）， with 10 rats in each group. Except for the control group， rats in all other groups were given mifepristone （8.3 mg/kg） and misoprostol （100 μg/kg） intragastrically to establish a threatened abortion model， and intragastric or intraperitoneal injection of corresponding drugs. The serum levels of estrogen， progesterone， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， and interleukin-4 （IL-4） in each group of rats were detected， and the uterine ovarian index and embryonic mortality rate of rats in each group were measured； the morphology of uterine tissue in rats was observed in each group； Th1/Th2 balance in peripheral blood of rats as well as the expression of PI3K/AKT signaling pathway-related proteins in the uterine tissues of rats in each group were detected. RESULTS Compared with the control group， the uterine tissue of rats in the model group showed pathological damage； the serum levels of estrogen， progesterone and IL-4， uterine ovarian index， peripheral blood Th2 cell ratio， and the ratios of phosphorylated PI3K （p-PI3K）/PI3K and phosphorylated AKT （p-AKT）/AKT in uterine tissue were all decreased （P＜0.05）； the embryo mortality rate， Th1 cell ratio， Th1/Th2 ratio， and serum levels of IFN-γ and TNF-α were increased （P＜0.05）. Compared with the model group， the pathological damage of uterine tissue in the A. sinensis polysaccharide group was reduced， and the above indexes were all improved significantly （P＜0.05）； LY294002 could weaken the effect of A. sinensis polysaccharide on model rats （P＜0.05）. CONCLUSIONS A. sinensis polysaccharides can improve Th1/Th2 imbalance in threatened abortion model rats by activating the PI3K/AKT signaling pathway， thereby inhibiting immune inflammation， and promoting embryo survival.