Liang Zhongshu, Leo Sunnar, Wen Helin, Ouyang Mao, Jiang Weihong, Yang Kan
Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People's Republic China.
BMC Cardiovasc Disord. 2015 May 13;15:42. doi: 10.1186/s12872-015-0030-4.
Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats.
Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis.
In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day.
(31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.
雷公藤甲素治疗可改善链脲佐菌素诱导的糖尿病大鼠模型中的糖尿病心肌病（DCM）。DCM的特征是心脏能量代谢异常。我们推测雷公藤甲素可改善DCM中的心脏代谢异常。我们提出采用磷-31核磁共振（³¹P NMR）光谱法评估体内心脏能量代谢，并评价雷公藤甲素治疗对DCM大鼠的影响。
对链脲佐菌素诱导的糖尿病大鼠分别进行为期六周的雷公藤甲素治疗，剂量分别为100、200或400μg/kg/天。将性别和年龄匹配的非糖尿病大鼠作为对照组。用超声心动图测定心腔大小和功能。用Krebs-Henseleit缓冲液灌注全心标本并进行³¹P NMR光谱分析。采用实时聚合酶链反应和蛋白质免疫印迹分析测定心脏p38丝裂原活化蛋白激酶（MAPK）。
糖尿病大鼠的心脏质量指数显著更高，而心脏射血分数低于对照组。³¹P NMR光谱显示糖尿病组的三磷酸腺苷（ATP）和磷酸肌酸（pCr）浓度也显著低于对照组。与未治疗的糖尿病大鼠相比，雷公藤甲素治疗的糖尿病组心脏质量指数显著降低，射血分数、ATP、pCr浓度及P38 MAPK表达更高。在接受200μg/kg/天剂量雷公藤甲素治疗的组中观察到最佳改善效果。
³¹P NMR光谱法能够评估全心标本中的心脏能量代谢。它可检测DCM心脏中的能量代谢异常。雷公藤甲素治疗至少部分通过上调MAPK信号转导改善心脏功能并增加心脏能量代谢。
