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您的检索式：作者名="Qiangyou Wan"
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| 1 | Congestive heart failure in COX2 deficient rats显示文摘Non-steroidal anti-inflammatory drugs(NSAIDs)inhibit prostaglandin(PG)formation by targeting cyclooxygenase(COX)1 and 2.Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events,cardiac failure,and hypertension.However,the underlying mechanisms remain unclear.In this study,COX1-and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting.DNA genotyping and Western blot analysis confirmed successful generation of COX1^(-/-) and COX2^(-/-) rats.Adult COX1^(-/-) rats grew normally,while more than 70%of COX2^(-/-) rats after wean died within 2 months.Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2^(-/-) rats compared to those in wildtype(WT)controls.Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2^(-/-)cardiac tissues.Moreover,cardiac ATP and acetyl-Co A production was dramatically decreased in COX2^(-/-) rats.Consistently,the expression of genes related to mitochondrial oxidation,such as those that encode for subunits of pyruvate dehydrogenase complex and acyl Co A dehydrogenases,were downregulated,while glycolytic hexokinase 1(HK1)was upregulated in COX2^(-/-) heart tissues.These observations indicate that COX2-deficient rats developed spontaneously heart failure,likely as a result of dysregulated cardiac energy metabolism. | Qiangyou Wan Deping Kong Qian Liu Shumin Guo Chenchen Wang Yan Zhao Zun-Ji Ke Ying Yu | 2021 | Science China(Life Sciences)2021，64，7： | 3 |
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