Hypertensive vascular remodeling was inhibited by Xuezhikang through the regulation of Fibulin-3 and MMPs in spontaneously hypertensive rats.
Hypertensive vascular remodeling was inhibited by Xuezhikang through the regulation of Fibulin-3 and MMPs in spontaneously hypertensive rats.
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血脂康通过调节自发性高血压大鼠的 Fibulin-3 和 MMPs 抑制高血压血管重塑。
DOI：
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Xiang Ding-Cheng
中科院分区：
文献类型：
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作者：
Lin Zhong-Wei;Wang Zhuo;Zhu Gui-Ping;Li Bo-Wei;Xie Wen-Lin;Xiang Ding-Cheng
纤维蛋白-3，一种细胞外糖蛋白，被认为在血管中有功能。在高血压患者中，细胞外基质、基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）在心血管重构中起重要作用。然而，纤维蛋白-3作为细胞外糖蛋白在高血压血管重构中的作用尚不清楚。我们的研究是为了确定fibuin -3和TIMPs/MMPs是否会影响高血压和血脂康治疗期间的血管结构。选取8周龄自发性高血压大鼠30只，随机分为3组：自发性高血压对照组（shs组，n=10）、低剂量血脂康组（XZK-L, 20 mg/kg/d, n=10）、高剂量血脂康组（XZK-H, 200 mg/kg/d, n=10），正常组10只，同年龄Wistar-Kyoto （WKY）大鼠。结果显示，对照组血清一氧化氮（NO）显著低于WKY组（P<0.05）。血清氧化低密度脂蛋白（ox-LDL）高于WKY组（P<0.05）。血之康高剂量组显著降低了ox-LDL、左心室质量指数（LVMI）和胸主动脉壁腔面积比（W/L） （P<0.05），血清NO显著升高（P<0.05）。免疫组化和western blot结果显示，与WKY组相比，SHRs组胸主动脉纤维蛋白-3和MMP-2、9蛋白和mRNA水平的表达均显著升高（P<0.05）。XZK-H组大鼠血清fibuin -3、MMP-2、9水平显著低于对照组（P<0.05）。SHRs组与WKY组间TIMP-3水平差异无统计学意义（P < 0.05）。血脂康对SHRs中Fibulin-3和mmp - 2,9水平有抑制作用。免疫组化结果显示，fibuin -3与MMP-2 （r=0.81， P<0.05）、MMP-9 （r=0.92， P<0.05）的转录本表达有较强的相关性。综上所述，fibuin -3和mmp - 2,9水平的过表达与高血压和血管重构有关，血脂康可抑制其表达。纤维蛋白-3是高血压患者心血管重构发病机制中的一个候选因子。
Fibulin-3, an extracellular glycoprotein, has been suggested as having functions in vessels. In hypertension, extracellular matrix, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important roles in cardiovascular remodeling. However, the role of Fibulin-3 as an extracellular glycoprotein in hypertensive vascular remodeling remains unclear. Our study was to determine whether Fibulin-3 and TIMPs/MMPs would affect vascular structure during hypertension and the treatment of Xuezhikang. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomized to three groups: SHRs control group (SHRs group, n=10), group treated with low dose Xuezhikang (XZK-L, 20 mg/kg/d, n=10) and group treated with high dose Xuezhikang (XZK-H, 200 mg/kg/d, n=10), the normal group was comprised of ten Wistar-Kyoto (WKY) rats of the same age. We showed that serum nitric oxide (NO) in control group was significantly lower than WKY group (P<0.05). Concomitantly, serum oxidized low-density lipoprotein (ox-LDL) was higher than WKY group (P<0.05). The treatment of high dose Xuezhikang significantly dicreased ox-LDL, left ventricular mass index (LVMI) and Wall-to-lumen area ratio (W/L) of thoracic aorta (P<0.05), while serum NO was significantly increasing (P<0.05). Moreover, the expressions of Fibulin-3 and MMP-2, 9 at both protein and mRNA levels were significantly higher in thoracic aorta of SHRs group compared to WKY group by immunohistochemistry and western blotting (P<0.05). However, the levels of Fibulin-3 and MMP-2, 9 were significantly decreased in XZK-H group compared to control group (P<0.05). The level of TIMP-3 had no significance difference between SHRs and WKY groups (P>0.05). So the levels of Fibulin-3 and MMP-2, 9 in SHRs could be inhibited by Xuezhikang. Furthermore, a strong correlation in transcript expression was established between Fibulin-3, and MMP-2 (r=0.81, P<0.05) and MMP-9 (r=0.92, P<0.05) through immunohistochemistry. In summary, the overexpression of Fibulin-3 and MMP-2, 9 levels were associated with hypertension and vascular remodeling and inhibited by Xuezhikang. Fibulin-3 is a candidate in the pathogenesis of cardiovascular remodeling in hypertension.
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影响因子：
20.1
作者：
Cho, A;Reidy, MA
通讯作者：
Reidy, MA
影响因子：
9.6
作者：
M. Roy;P. Carey
通讯作者：
M. Roy;P. Carey
DOI：
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发表时间：
2011-12
期刊：
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine
影响因子：
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作者：
F. Jiang;Li-ping Sun;J. Yang
通讯作者：
F. Jiang;Li-ping Sun;J. Yang
影响因子：
--
作者：
Birkedal-Hansen, Henning;Yamada, Susan;Birkedal-Hansen, Bente
通讯作者：
Birkedal-Hansen, Bente
影响因子：
--
作者：
Vargova, Viola;Pytliak, Marek;Mechirova, Viola
通讯作者：
Mechirova, Viola