Niaspan attenuates the adverse effects of bone marrow stromal cell treatment of stroke in type one diabetic rats.
Niaspan attenuates the adverse effects of bone marrow stromal cell treatment of stroke in type one diabetic rats.
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DOI：
10.1371/journal.pone.0081199
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Yan T;Ye X;Chopp M;Zacharek A;Ning R;Venkat P;Roberts C;Lu M;Chen J
我们以前的研究发现，骨髓基质细胞（BMSC）治疗可改善非糖尿病大鼠卒中后的功能恢复，同时增加1型糖尿病（T1 DM）大鼠的脑出血并诱导动脉硬化样变化。Niaspan治疗卒中可增加T1 DM大鼠的血管稳定性，减少脑出血和血脑屏障（BBB）渗漏。因此，我们测试了BMSC与Niaspan的组合疗法减弱T1 DM大鼠中BMSC单一疗法的副作用的假设。对链脲佐菌素诱导的T1 DM大鼠进行2小时的大脑中动脉闭塞（MCAo），并在MCAo后24小时开始用以下药物治疗：1）PBS; 2）BMSC（5×106）; 3）Niaspan（40 mg/kg，每日一次，持续14天; 4）BMSC（5×106）+Niaspan（40 mg/kg，每日一次，持续14天）组合。所有大鼠均监测14天。与非治疗对照和BMSC单一治疗动物相比，T1 DM-MCAo大鼠的BMSC+Niaspan组合治疗没有增加脑出血，并且显著降低了BBB渗漏和血管动脉硬化样变化，以及降低了缺血脑和颈内动脉中的血管生成素、基质金属蛋白酶9（MMP 9）和ED 1表达。使用BMSC与Niaspan的联合治疗减少了BBB渗漏和脑动脉硬化样变化。这些有益作用可能归因于血管生成素、MMP 9和ED 1的表达降低。
Our previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats. T1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×106); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×106) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days. Combination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals. Combination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.