糖尿病大鼠心脏纤维化的治疗；过氧化物酶体增殖物激活受体γ（PPAR-γ）和钙通道阻滞剂（CCBs）的作用。
Management of cardiac fibrosis in diabetic rats; the role of peroxisome proliferator activated receptor gamma (PPAR-gamma) and calcium channel blockers (CCBs).
机构信息
Department of Biochemistry, Faculty of Pharmacy, October for Modern Science and Arts University (MSA), Egypt.
出版信息
Diabetol Metab Syndr. 2011 Mar 30;3(1):4. doi: 10.1186/1758-5996-3-4.
BACKGROUND
Diabetes mellitus (DM) and hypertension (HTN) are accused of being responsible for the development of the cardiac fibrosis due to severe cardiomyopathy.
METHODS
Blood glucose (BG) test was carried out, lipid concentrations, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), matrix metalloproteinase (MMP-2), collagen-I and collagen-III were measured in male Albino rats weighing 179-219 g. The rats were divided into five groups, kept on either control diet or high fat diet (HFD), and simultaneously treated with rosiglitazone (PPAR-gamma) only for one group with 3 mg/kg/day via oral route for 30 days, and with rosiglitazone and felodipine combination for another group with 3 mg/kg/day and 5 mg/kg/day, respectively via oral route for 30 days.
RESULTS
Diabetic hypertensive (DH) rats which fed on a HFD, injected with streptozotocin (STZ) (i.p.) and obstruction for its right kidney was occurred develop hyperglycemia, hypertension, cardiac fibrosis, hypertriglyceridemia, hypercholesterolemia, increased TNF-α, increased TGF-β, decreased MMP-2, increased collagen-I and increased collagen-III, when compared to rats fed on control diet. Treating the DH rats with rosiglitazone only causes a significant decrease for BG levels by 52.79%, triglycerides (TGs) by 24.05%, total cholesterol (T-Chol) by 30.23%, low density lipoprotein cholesterol (LDL-C) by 40.53%, TNF-α by 20.81%, TGF-β by 46.54%, collagen-I by 48.11% and collagen-III by 53.85% but causes a significant increase for MMP-2 by 272.73%. Moreover, Treating the DH rats with rosiglitazone and felodipine combination causes a significant decrease for BG levels by 61.08%, blood pressure (BP) by 16.78%, TGs by 23.80%, T-Chol by 33.27%, LDL-C by 45.18%, TNF-α by 22.82%, TGF-β by 49.31%, collagen-I by 64.15% and collagen-III by 53.85% but causes a significant increase for MMP-2 by 290.91%. Rosiglitazone alone failed to decrease the BP in DH rats in the current dosage and duration.
CONCLUSION
Our results indicate that the co-existence of diabetes and hypertension could induce cardiomyopathy which could further result in cardiac fibrosis, and that combination treatment with rosiglitazone and felodipine has a great protective role against the metabolic abnormalities, meanwhile, the treatment with rosiglitazone alone has a protective role with a minimal effect against these abnormalities and has no effect on decreasing BP in these cases which may lead to coronary artery diseases (CADs) in future.
背景
糖尿病（DM）和高血压（HTN）被认为是由于严重的心肌病导致心脏纤维化发展的罪魁祸首。
方法
对体重为 179-219g 的雄性白化大鼠进行血糖（BG）测试，测量血脂浓度、肿瘤坏死因子 alpha（TNF-α）、转化生长因子 beta（TGF-β）、基质金属蛋白酶（MMP-2）、胶原-I 和胶原-III。大鼠分为五组，分别给予对照饮食或高脂肪饮食（HFD），同时给予罗格列酮（PPAR-γ）治疗一组，每天 3mg/kg 口服，连续 30 天，给予罗格列酮和非洛地平联合治疗一组，剂量分别为 3mg/kg 和 5mg/kg 口服，连续 30 天。
结果
糖尿病高血压（DH）大鼠，给予高脂肪饮食，链脲佐菌素（STZ）（ip）注射，并阻塞其右肾，导致高血糖、高血压、心脏纤维化、高三酰甘油血症、高胆固醇血症、TNF-α 增加、TGF-β 增加、MMP-2 减少、胶原-I 增加和胶原-III 增加，与给予对照饮食的大鼠相比。仅用罗格列酮治疗 DH 大鼠可使 BG 水平显著降低 52.79%，甘油三酯（TGs）降低 24.05%，总胆固醇（T-Chol）降低 30.23%，低密度脂蛋白胆固醇（LDL-C）降低 40.53%，TNF-α 降低 20.81%，TGF-β 降低 46.54%，胶原-I 降低 48.11%，胶原-III 降低 53.85%，但 MMP-2 增加 272.73%。此外，用罗格列酮和非洛地平联合治疗 DH 大鼠可使 BG 水平显著降低 61.08%，血压（BP）降低 16.78%，TGs 降低 23.80%，T-Chol 降低 33.27%，LDL-C 降低 45.18%，TNF-α 降低 22.82%，TGF-β 降低 49.31%，胶原-I 降低 64.15%，胶原-III 降低 53.85%，但 MMP-2 增加 290.91%。在目前的剂量和时间内，罗格列酮单独治疗不能降低 DH 大鼠的血压。
结论
我们的结果表明，糖尿病和高血压的共存可导致心肌病，进而导致心脏纤维化，罗格列酮和非洛地平联合治疗对代谢异常具有很好的保护作用，同时，单独使用罗格列酮治疗对这些异常具有保护作用，对这些异常的影响最小，对降低这些情况下的血压没有影响，这可能导致未来的冠状动脉疾病（CADs）。
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