瑞舒伐他汀对大鼠颈总动脉球囊损伤后内膜增生和PTEN表达的影响
《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]
- 期数:
- 2009年第3期
- 页码:
- 309-312
- 栏目:
- 基础研究
- 出版日期:
- 2009-05-15
文章信息/Info
- Title:
- Effect of rosuvastatin on neointimal hyperplasia and PTEN expression of rat carotid artery after balloon injury
- Author(s):
- DONG Shao-hong; ZENG Chun-miao; LIU Hua-dong; LI Peng
- Department of Cardiology, Shenzhen people’s Hospital, Second Clinic Medical College of Jinan University, Shenzhen 5l8020, Guangdong, China
- Keywords:
- Rosuvastatin; Neointimal hyperplasia; Balloon injury; Rats; PTEN
- 分类号:
- R543；R654
- DOI:
- -
- 文献标识码:
- A
- 摘要:
- 目的 观察瑞舒伐他汀对大鼠颈总动脉损伤后内膜增生及总PTEN、P-PTEN蛋白表达的影响。方法 将48只雄性SD大鼠随机分为组A和组B，每组24只。两组分别建立大鼠左颈总动脉球囊损伤模型。其中组A和组B均取左颈总动脉（行球囊损伤侧）分别作为损伤组和治疗组，另取组A的右颈总动脉（未行球囊损伤侧）作为正常对照组。组B于损伤前3 d始连续每天给予瑞舒伐他汀5 mg/(kg·d)灌胃，组A予9 g/L氯化钠溶液灌胃。组A和组B大鼠分别于建模后7 d或14 d，取颈总动脉制做病理切片观察动脉内膜增生。用Western blot检测总PTEN和P-PTEN蛋白的表达。结果 共40只大鼠完成本实验。①与正常对照组比较，血管损伤后7 d，新生内膜形成，损伤14 d内膜面积、内膜/中膜面积的比值增大，管腔面积明显减少（与正常对照组比较，P<0.05）。损伤后14 d，治疗组的管腔面积较损伤组增加26％（P<0.05）。②损伤组总PTEN和P-PTEN的表达均较正常对照组增高，P-PTEN/总PTEN的比值增大（P<0.05）。治疗组P-PTEN/总PTEN的比值较损伤组明显降低（P<0.05）。结论 ①瑞舒伐他汀可抑制大鼠颈动脉球囊损伤后内膜增生。②瑞舒伐他汀可降低P-PTEN/总PTEN的比值。③此二项作用可能具有相关性。
- Abstract:
- AIM To study the effect of Rosuvastatin on intimal hyperplasia and PTEN expression changes after balloon catheter injury in rat carotid artery. METHODS 48 male SPF SD rats were equally divided into Group A and Group B, and then subjected to balloon catheter injury on the left carotid artery. Group B rats were given Rosuvastatin(dissolved in Nacl, gavage) at the dosage of 5 mg/(kg·d) 3 days before the injury, while Group A rats were given vehicle instead. The left carotid arteries of both Group A and Group B rats were respectively defined as the injured group and the Rosuvastatin group, then the right artery of Group A as normal control. Both Group A and Group B rats were sacrificed at 7 days or 14 days after injury, and Both sides of common carotid arteries were harvested. Intimal hyperplasia and the expression of total PTEN and P-PTEN protein were determined by HE staining and Western blot analysis. RESULTS Forty rats were included. ①Neointimal formation was observed on 7th day after balloon injury and increased intimal area became significant in 14 d injured group, accompanied with increased area ratio of intimal/media and reduced lumen area (compared with normal control group, P<0.05). Lumen area in 14 d Rosuvastatin group increased by 26% than that in 14 d injured group（P<0.05）. ②The expression of total PTEN, and phosphoPTEN and the ratio of phosphoPTEN/total PTEN increased in injured group compared with the normal control group(P<0.05). However, that ratio decreased significantly in Rosuvastatin group compared with that the injured group (P<0.05). CONCLUSION ①Rosuvastatin could inhibit intimal hyperplasia of rat carotid artery after balloon injury. ②Rosuvastatin could decrease the ratio of phosphoPTEN/total PTEN. ③There might be some relativity between these two aspects above.
参考文献/References
[1］ Saito Y, Swanson X, Mhashilkar AM, et al. Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo［J］. Gene therapy, 2003, 10(23):1961-1969.
［2］ Mourani PM, Garl PJ, Wenzlau JM, et al. Unique, highly proliferative growth phenotype expressed by embryonic and neointimal smooth muscle cells is driven by constitutive Akt, mTOR, and p70S6K signaling and is actively repressed by PTEN［J］. Circulation, 2004, 109(10):1299-1306.
［3］ van der Harst P, Groenewegen HC, Roks AJ, et al. Rosuvastatin attenuates angiotensin II-induced neointimal formation after stent implantation in the rat［J］. Coronary Artery Disease, 2008, 19(1):47-53.
［4］ Huang J, Kontos CD. Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN［J］. Arterioscle Thromb Vasc Biol, 2002, 22(5):745-751.
［5］ Huang J, Niu XL, Pippen AM, et al. Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia［J］. Arterioscler Thromb Vasc Biol, 2005, 25(2):354-358.
［6］ Garl PJ, Wenzlau JM, Walker HA, et al. Perlecan-Induced Suppression of Smooth Muscle Cell Proliferation Is Mediated Through Increased Activity of the Tumor Suppressor PTEN［J］. Circ Res, 2004, 94(2):175-183.
［7］ Kiyan J, Kusch A, Tkachuk S, et al. Rosuvastatin regulates vascular smooth muscle cell phenotypic modulation in vascular remodeling: Role for the urokinase receptor［J］. Atherosclerosis, 2007, 195（2）:254-261.
［8］ Teresi RE, Planchon SM, Waite KA, et al. Regulation of the PTEN promoter by statins and SREBP［J］. Human Molecular Genetics, 2008, 17(7): 919-928.
备注/Memo
- 备注/Memo:
- 收稿日期：2008-10-17.通讯作者：董少红，主任医师，博士，主要从事冠心病与高血压病诊治及介入心脏病的研究Email:Dsh266@medmail.com.cn
常用功能
统计/Statistics
- 摘要浏览/Viewed1613
- 评论/Comments
