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基于Notch信号通路的黄芩素抑制急性肺栓塞模型大鼠血小板聚集及肺组织保护作用机制研究
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| 篇名： | 基于Notch信号通路的黄芩素抑制急性肺栓塞模型大鼠血小板聚集及肺组织保护作用机制研究 |
| TITLE： | Study on Mechanism of Platelet Aggregation Inhibitory Effects and Lung Tissue Protective Effects of Baicalein in Model Rats with Acute Pulmonary Embolism Based on Notch Signaling Pathway |
| 摘要： | 目的：探索黄芩素抑制急性肺栓塞模型大鼠血小板聚集及肺组织保护作用的机制。方法：将36只大鼠随机分为正常对照组（n＝6）和造模组（n＝30），造模组大鼠采用自体血栓法复制急性肺栓塞模型，正常对照组大鼠行假手术。将造模成功的30只大鼠随机分为模型对照组、阳性药物组（低分子肝素钙0.01mL/kg，皮下注射）和黄芩素低、中、高剂量组（25、50、100mg/kg，腹腔注射），每组6只。正常对照组和模型对照组大鼠腹腔注射等体积生理盐水，各给药组大鼠给予相应药物，每天1次，连续给药7d。给药结束后，检测大鼠血浆二磷酸腺苷（ADP）和花生四烯酸（AA）活化后的血小板聚集率及血小板活化指数（RPI）；采用苏木精-伊红染色法观察大鼠肺组织病理学变化；采用酶联免疫吸附法检测大鼠血清中血小板活化标志物血小板颗粒膜蛋白（CD62P）和溶酶体颗粒膜蛋白（CD63）以及生长分化因子15（GDF-15）、N端B型利钠肽（NT-proBNP）水平；采用实时荧光定量聚合酶链式反应法检测大鼠肺组织中Notch2、Notch3及Notch信号配体DLL1、JAG2mRNA表达水平；分别采用免疫组化法和Westernblotting法检测大鼠肺组织中Notch2、Notch3、DLL1、JAG2蛋白表达水平。结果：与正常对照组比较，模型对照组大鼠血浆ADP活化后血小板聚集率、AA活化后血小板聚集率、RPI值以及血清中CD62P、CD63、GDF-15、NT-proBNP水平均显著升高（P＜0.05）；肺组织处于严重炎性浸润状态；肺组织中Notch2、Notch3、DLL1、JAG2mRNA及蛋白表达水平均显著降低（P＜0.05）。与模型对照组比较，黄芩素各剂量组大鼠上述指标变化均显著改善（P＜0.05）。结论：黄芩素能够降低急性肺栓塞模型大鼠血小板聚集，改善大鼠肺组织病理状态；其机制可能与激活Notch信号通路有关。 |
| ABSTRACT： | OBJECTIVE：To explore the mec hanism of baicalein plat elet aggregation inhibitiory effect and lung tissue protective effect of baicalein in model rats with acute pulmonary embolism. METHODS ：Totally 36 rats were randomly divided into normal control group （n＝6）and modeling group （n＝30）. The acute pulmonary embolism model was established by autologous thrombus replication in modeling group ，and the sham operation of rats in normal control group was carried out. After modeling ， 30 model rats were randomly divided into model control group ，positive drug group （low molecular weight heparin calcium 0.01 mL/kg，subcutaneous injection ），baicalein low-dose ，middle-dose and high-dose groups （25，50，100 mg/kg，intraperitoneal injection），with 6 rats in each group. Normal control group and model control group were intraperitoneally injected constant volume of normal saline ；administration groups were given relevant medicine ，once a day ，for consecutive 7 d. After medication ， platelet aggregation rates of rats after activated with adenosine diphosphate （ADP） and arachidonic acid （AA） and platelet activation index （RPI）were detected ；lung histopathology was observed by HE staining ；serum platelet activation markers granule membrane（CD62P）and lysosomal membrane glycoprotein （CD63），growth differentiation factor- 15（GDF-15）and N-terminal B-type natriuretic peptide （NT-proBNP）were measured by ELISA. The mRNA expression levels of Notch 2，Notch3 and Notch signaling ligand PLL 1，JAG2 were detected by RT-PCR method. The protein expression levels of Notch 2，Notch3，DLL1 and JAG2 in lung tissue were detected by immunohistochemistry and Western blotting assay. RESULTS ：Compared with normal control group，plasma ADP-activated platelet aggregation rate ，AA-activated platelet aggregation rate ，RPI，serum levels of CD 62P， CD63，GDF-15 and NT-proBNP were increased significantly （P＜0.05）. The lung tissue of rats was in a state of severe inflammatory infiltration. mRNA and protein expression levels of Notch 2，Notch3，DLL1 and JAG 2 in lung tissue decreased significantly（P＜0.05）. Compared with model control group ，changes of above indexes of rats were improved significantly in baicalein groups （P＜0.05）. CONCLUSIONS ：Baicalein can reduce platelet aggregation and improve the pathological state of lung tissue in rats with acute pulmonary embolism. Its mechanism 0270） may be related to activating Notch signal pathway. |
| 期刊： | 2020年第31卷第09期 |
| 作者： | 吴忠勇，王金忠，周森，林明，王小智 |
| AUTHORS： | WU Zhongyong，WANG Jinzhong，ZHOU Sen，LIN Ming，WANG Xiaozhi |
| 关键字： | 黄芩素；急性肺栓塞；Notch信号通路；血小板聚集；大鼠；机制 |
| KEYWORDS： | Baicalein； Acute pulmonary embolism ； |
| 阅读数： | 271 次 |
| 本月下载数： | 9 次 |
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