阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响

doi:10.13418/j.issn.1001-165x.2020.06.012

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (6) : 685-690. DOI: 10.13418/j.issn.1001-165x.2020.06.012

实验研究

阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响

汤银娟¹，　罗华²，　朱国富³，　蔡维君⁴，　罗明英⁵

作者信息 +

The effect of atorvastatin on the collateral vessel growth in hypercholesterolemia rats

TANG Yin-juan¹, LUO Hua², ZHU Guo-fu³, CAI Wei-jun⁴, LUO Ming-ying⁵

Author information +

文章历史 +

摘要

目的　探讨阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响。方法　28只成年SD大鼠，给予高脂饮食8周，建立结扎股动脉诱导的高胆固醇血症大鼠侧支血管生长模型。随机将动物分为单纯股动脉结扎组（L组）、高胆固醇血症+股动脉结扎组（HL组）和阿托伐他汀（0.3 mg·kg-1·14 d-1，腹腔注射）+高胆固醇血症+股动脉结扎组（AL组）。存活7 d后，采用血管造影，HE染色和共聚焦免疫荧光术，观察高胆固醇血症情况下，阿托伐他汀应用对侧支血管生长的作用以及重要的促侧支血管生长分子在侧支血管表达模式的变化。结果　与L组比较，HL组的侧支血管数目减少，侧支血管生长受到损害，表现为血管内膜过度增生，中膜明显增厚，导致血管腔狭窄，且血管壁细胞增殖和外膜炎症细胞减少；AL组应用了阿托伐他汀，侧支血管的生长较HL组明显改善，发育为管腔较大的侧支血管，血管壁细胞的增殖和外膜炎症细胞增多，侧支血管数目增加。其侧支血管数目，血管横截面积和免疫荧光强度差异具有统计学意义（P<0.05）。结论　高胆固醇血症损害大鼠后肢侧支血管的生长；阿托伐他汀可促进血管壁细胞的增殖和外膜巨噬细胞的增多，从而改善和恢复侧支血管的生长。

Abstract

Objective To investigate the effect of atorvastatin on the collateral vessel growth in hypercholesterolemia rats.　Methods　Twenty-eight adult SD rats were given a high-fat diet for 8 weeks, to establish a model of collateral vessel growth induced by ligature of femoral artery in hypercholesterolemia rats hind limb. Rats were randomly divided into a ligation-only group (L group), a hypercholesterolemia + ligation group (HL group), and an atorvastatin (0.3mg/kg/2w, intraperitoneal injection) + hypercholesterolemia + ligation group (AL group). After a 7-day survival, the effects of atorvastatin on collateral vessel growth and the change of the expression pattern of important cytokines were detected by angiography, HE staining, and confocal immunofluorescence.　Results　Compared with the L group, the number of collateral vessels in the HL group reduced, and the collateral vessels growth was impaired, showing that the intimal hyperplasia was manifested and the tunica media was significantly thickened, resulting in narrowing of the vascular lumen, and cell proliferation of the vascular wall and decreasing of the adventitia inflammatory cells. Compared with the HL group, after the application of atorvastatin in the AL group, the growth of collateral vessels significantly improved, and developed into collateral vessels with a larger lumen. The cell proliferation of vascular wall, the adventitia inflammatory cells, and the number of visible collateral vessels all increased. There were statistical significance among the number of collateral vessels, cross sectional area of collateral vessels and the immunofluorescence intensity difference (P<0.05). Conclusions　Hypercholestero- lemia impairs the growth of collateral vessels in the rat hind limbs. Atorvastatin can improve the proliferation of vascular wall cells and the increasing of adventitia macrophage cells, resulting in promoting and restoring the growth of collateral vessels.

导出引用

汤银娟, 罗华, 朱国富, 蔡维君, 罗明英. 阿托伐他汀对高胆固醇血症大鼠侧支血管生长的影响[J]. 中国临床解剖学杂志. 2020, 38(6): 685-690 https://doi.org/10.13418/j.issn.1001-165x.2020.06.012

TANG Yin-juan, LUO Hua, ZHU Guo-fu, CAI Wei-jun, LUO Ming-ying. The effect of atorvastatin on the collateral vessel growth in hypercholesterolemia rats[J]. Chinese Journal of Clinical Anatomy. 2020, 38(6): 685-690 https://doi.org/10.13418/j.issn.1001-165x.2020.06.012

中图分类号： R322.12

参考文献

[1] Jamaiyar A, Juguilon C, Dong F, et al. Cardioprotection during ischemia by coronary collateral growth[J]. Am J Physiol Heart Circ Physiol, 2019, 316 (1): H1-H9.
[2] Budatha M, Zhang JS, Zhuang ZW, et al. Inhibiting integrin α5 cytoplasmic domain signaling reduces atherosclerosis and promotes arteriogenesis[J]. J Am Heart Assoc, 2018, 7(3): e007501.
[3] Ajayi NO, Vanker EA, Satyapal KS. Coronary artery dominance dependent collateral development in the human heart[J]. Folia Morphol (Warsz), 2017, 76(2): 191-196.
[4] Tirziu D, Moodie KL, Zhuang ZW, et al. Delayed arteriogenesis in hypercholesterolemic mice[J]. Circulation, 2005, 112(16): 2501-2509.
[5] Wang D, Li T, Wei HJ, et al. Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model[J]. J Neurol Sci, 2016, 362: 91-99.
[6] Chiang KH, Cheng WL, Shih CM, et al. Statins, HMG-CoA reductase inhibitors, improve neovascularization by increasing the expression density of CXCR4 in endothelial progenitor cells [J]. PLoS One, 2015, 10(8): e0136405.
[7] Rizzi A, Benagiano V, Ribatti D. Angiogenesis versus arteriogenesis[J]. Rom J Morphol Embryol, 2017, 58(1): 15-19.
[8] van Weel V, de Vries M, Voshol PJ, et al. Hypecholesterolemia reduces collateral artery growth more dominantly than hyperglycemia or insulin resistance in mice[J]. Arterioscler Thromb Vasc Biol, 2006, 26(6): 1383-1390.
[9] Bucay M, Nguy J, Barrios R, et al. Impaired adaptive vascular growth in hypercholesterolemic rabbit[J]. Atherosclerosis, 1998, 139(2): 243-251.
[10] Tang YJ, Wang JJ, Guan YL, et al. Effect of atorvastatin on LOX-1 and eNOS expression in collateral vessels of hypercholesterolemic rats[J]. J South Med Univ, 2019, 39(11): 1265-1272.
[11]Maron DJ, Fazio S, Linto MF. Current perspectives on statins[J]. Circulation, 2000, 101(2): 207-213.
[12]Diamantis E, Kyriakos G, Quiles-Sanchez LV, et al. The anti-inflammatory effects of statins on coronary artery disease: an updated review of the literature[J]. Curr Cardiol Rev, 2017, 13(3): 209-216.
[13] Wang XL, Qi J, Shi YQ, et al. Atorvastatin plus therapeutic ultrasound improve postnatal neovascularization in response to hindlimb ischemia via the PI3K-Akt pathway[J]. Am J Transl Res, 2019, 11(5): 2877-2886.
[14]Goggi JL, Ng M, Shenoy N, et al. Simvastatin augments revascularization and reperfusion in a murine model of hind limb ischemia-Multimodal imaging assessment[J]. Nucl Med Biol, 2017, 46: 25-31.