Guo Xin, Xue Mei, Li Chun-Jun, Yang Wei, Wang Shan-Shan, Ma Ze-Jun, Zhang Xiao-Na, Wang Xiao-Yu, Zhao Ran, Chang Bao-Cheng, Chen Li-Ming
Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China.
Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China.
J Ethnopharmacol. 2016 Dec 4;193:333-344. doi: 10.1016/j.jep.2016.08.029. Epub 2016 Aug 21.
Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects.
In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function.
Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200μg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining.
In the diabetic group, the expressions of TLR4 and NF-κB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-κB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-α, IL-1β), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including α-SMA, TGF-β1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups.
Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-κB/IL-1β immune pathway, suppression of NF-κB/TNF-α/VCAM-1 inflammatory pathway and down-regulation of TGF-β1/α-SMA/Vimentin fibrosis pathway.
雷公藤甲素是从传统中药雷公藤中提取的一种极为重要的活性成分，因其具有免疫抑制、抗增殖和抗炎作用，已被广泛用于治疗肾小球肾炎以及免疫介导的疾病。
在本研究中，我们研究了雷公藤甲素通过调节免疫系统、减轻炎症反应，从而减少心脏纤维化并改善左心室功能，对糖尿病性心肌病（DCM）的潜在保护作用。
将Sprague-Dawley大鼠随机分为5组：正常组、糖尿病组以及用雷公藤甲素（分别为50、100或200μg/kg/天）治疗8周的糖尿病大鼠组。通过超声心动图评估心脏功能，并用苏木精-伊红（HE）染色、Masson染色和扫描电子显微镜检查心脏的组织病理学。通过逆转录-聚合酶链反应（RT-PCR）、蛋白质免疫印迹法（Western blot）和免疫组织化学染色检测免疫调节介质、巨噬细胞浸润、炎症反应和心脏纤维化相关细胞因子。
在糖尿病组中，Toll样受体4（TLR4）和核因子κB p65（NF-κB p65）的表达均上调，这与促炎细胞因子增加、心脏纤维化以及左心室功能受损有关。有趣的是，雷公藤甲素治疗组的左心室病理结构和功能均得到显著改善。此外，与糖尿病组相比，中、高剂量雷公藤甲素治疗时，免疫介质TLR4、下游激活剂NF-κB p65、巨噬细胞浸润（CD68+）、促炎细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β））、细胞粘附分子（血管细胞粘附分子-1（VCAM-1））和趋化因子（单核细胞趋化蛋白-1（MCP-1））均受到显著抑制。此外，在雷公藤甲素治疗组中，观察到包括α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）、波形蛋白和胶原蛋白积累在内的心脏纤维化途径明显减少。
我们的数据表明，雷公藤甲素对DCM的保护作用可能归因于抑制TLR4诱导的NF-κB/IL-1β免疫途径、抑制NF-κB/TNF-α/VCAM-1炎症途径以及下调TGF-β1/α-SMA/波形蛋白纤维化途径。
