高血壓(hypertension)是一種慢性的發炎疾病。其致病機轉為血管內產生發炎反應、引起內皮細胞受損以及平滑肌細胞的增生與遷徙而導致了血管的重組(vascular remodeling)。血管結構重組後，由於血管的彈性喪失促使血管收縮的能力受到限制，進而導致血壓持續的攀升。介白素-20 (Interleukin-20，IL-20)屬於IL-10 家族的一員，是一種趨發炎性的細胞激素(pro-inflammatory cytokine)。先前的文獻指出，IL-20會直接或是間接地影響內皮細胞的血管新生，進而促進動脈粥狀硬化的發生。由實驗可以發現，在自發性高血壓老鼠(SHR)的血清中IL-20的表達量比對照組的老鼠(WKY)來得高。因此我的研究目的是想探討IL-20是否在血管的平滑肌細胞(vascular smooth muscle cells，VSMCs)扮演重要角色而參與高血壓的發病過程。首先，我們利用RT-PCR的方式分析IL-20以及其接受器(IL-20R1/ IL-20R2以及IL-22R1/ IL-20R2)在SHR與WKY的VSMCs的表現，証實VSMCs的確可以作為IL-20的標的細胞。接著我們利用MTT assay、ROS assay以及遷徙實驗(migration assay)去檢視IL-20對VSMCs的影響。結果顯示，IL-20對於VSMCs的增生以及ROS的生成沒有明顯的影響。但是IL-20會促使VSMCs產生更高的TNF-α以及IL-6等被認為是高血壓的危險因子。再者IL-20經由活化ERK1/2和STAT-3，正向調節IGF以及負向調節E-cadherin進而增強SHR VSMCs的遷徙能力，然而對WKY VSMCs則沒有顯著的差異。以上的實驗結果，我們推論IL-20可能經由刺激SHR VSMCs的遷徙以及發炎反應而參與在高血壓的致病機轉之中。

Hypertension is characterized by the remodeling of arterial wall. This remodeling involves changes in arterial wall components leading to arterial stiffness, which is induced by inflammation, endothelium dysfunction and hypertrophy of vascular smooth muscle cells (VSMCs). All promote vasoconstriction and create a situation ripe for establishment of atherosclerotic plaques. Interleukin-20 (IL-20) belongs to IL-10 family and is a proinflammatory cytokine. Previous studies showed that IL-20 has both direct and indirect angiogenic effects on endothelial cells to promote the progression of atherosclerosis. In this study, we found that IL-20 in the serum of spontaneous hypertension rat (SHR) is higher than that of healthy control (WKY). Therefore, we were aimed to explore the roles of IL-20 in VSMCs involved in the pathogenesis of hypertension. We analyzed the expression of IL-20 and its receptor complex, IL-20R1/R2 and IL-20R2/IL-22R1, in VSMCs isolated from spontaneous hypertension rats (SHR) and control rats (Wistar Kyoto, WKY) by using RT-PCR. Then, we performed MTT assay, ROS assay and migration assay to examine the effects of IL-20 on VSMCs. Our results showed that both VSMCs could be the target cells of IL-20 due to the expression of its receptors on these cells. IL-20 had no significant effect on proliferation and ROS production in VSMCs. However, IL-20 induced the migration of SHR VSMCs through ERK1/2 and STAT-3 pathway. Moreover, in response to IL-20, SHR VSMCs produced TNF-α and IL-1two important risk factors involved in hypertension. In addition, IL-20 induced cell migration of SHR VSMCs through up-regulation of IGF and down-regulation of E-cadherin. Taken together, IL-20 may be involved in enhancing migration of vascular smooth muscle cells and inducing inflammatory response in spontaneous hypertension rat model.

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