Credit Shontell L, Benghuzzi Hamed A, Tucci Michelle, Farah Ibrahim, Cameron Joseph A
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Biomed Sci Instrum. 2002;38:95-100.
Studies have shown that endogenous estrogen minimized cellular injury at the organ level; however, very little research was done to determine the effects of endogenous androgens such as Testosterone (T), Dihydrotestosterone, (DHT), and Androstenedione (AED) on the cardiovascular system at the cellular level Studies targeted at establishing such effects will broaden our understanding of the roles played by these male steroid hormones on the cardiovascular system. Our objective therefore was to (1) Use a Rat model and sustained delivery of physiological levels of these hormones to (1) evaluate pathophysiological effects on the cardiovascular system; and (2) localized cytokines such as IL-1, IL-6 and TNF on these tissues. Four groups of Sprague Dawley rats were included in the study. Group 1 animals served as control, groups II, III, and IV were treated with TCPL drug delivery devices containing 40 mg each of T, DHT, and AED, respectfully. Animals were sacrificed after 90 days of exposure. The ventricles and apex were immunostained for IL-1, IL-6, TNF and were also stained with Hemotoxylin and Eosin for histopathological evaluation. Results showed that TCPL drug delivery systems released 5 ng/ml/day of T, and 2 ng/ml/day of DHT and AED. IL-6 was expressed in the control heart ventricle and T, DHT, and AED reduced expression of the cytokine significantly after 90 days. Very small number of cells from the apex responded to IL-6 than cells within the ventricles. The results revealed that (i) the exposure of sustained levels of androgenic hormones exhibited myocardial hypertrophic condition compared to the control animals, (ii) the control animals had a two-fold increase in the ventricles IL-6 production over T treated animals and approximately five-fold increase over DHT and AED treated animals, and (iii) other inflammatory cytokines IL-1 and TNF were not differentially expressed in the ventricles of experimental animals when compared with the control; and (iv) In the apex tissue, animals treated with AED exhibited cells with increased response to IL-6 and a decrease cells responding to TNF and IL-1. IL-6 production in the ventricles decreased in animals exposed to sustained androgenic steroids and this decrease could possibly lead to increased blood flow, resulting in better oxygenation of the myocardium and improved cardiac function.
研究表明，内源性雌激素可将器官水平的细胞损伤降至最低；然而，关于内源性雄激素如睾酮（T）、双氢睾酮（DHT）和雄烯二酮（AED）在细胞水平对心血管系统影响的研究却很少。旨在确定此类影响的研究将拓宽我们对这些雄性类固醇激素在心血管系统中所起作用的理解。因此，我们的目标是：（1）使用大鼠模型并持续递送这些激素的生理水平，以（1）评估对心血管系统的病理生理影响；以及（2）定位这些组织上的细胞因子，如白细胞介素 -1（IL-1）、白细胞介素 -6（IL-6）和肿瘤坏死因子（TNF）。该研究纳入了四组斯普拉格 - 道利大鼠。第1组动物作为对照，第II、III和IV组分别用含有40毫克T、DHT和AED的TCPL药物递送装置进行治疗。暴露90天后对动物实施安乐死。对心室和心尖进行IL-1、IL-6、TNF免疫染色，并用苏木精和伊红染色进行组织病理学评估。结果显示，TCPL药物递送系统每天释放5纳克/毫升的T、2纳克/毫升的DHT和AED。IL-6在对照心脏心室中表达，90天后T、DHT和AED显著降低了该细胞因子的表达。与心室内的细胞相比，来自心尖的细胞对IL-6产生反应的数量非常少。结果表明：（i）与对照动物相比，持续暴露于雄激素水平会出现心肌肥厚状况；（ii）对照动物的心室内IL-6产生量比T处理的动物增加了两倍，比DHT和AED处理的动物增加了约五倍；（iii）与对照相比，实验动物心室内其他炎性细胞因子IL-1和TNF没有差异表达；以及（iv）在心尖组织中，AED处理的动物表现出对IL-6反应增加的细胞，对TNF和IL-1反应的细胞减少。暴露于持续雄激素类固醇激素的动物心室内IL-6产生量减少，这种减少可能导致血流量增加，从而使心肌氧合更好，心脏功能得到改善。
