高氏柴胡製備小柴胡湯對糖尿病腎病變之保健功效評估
葉靜華
長榮大學醫研究所
糖尿病腎病變已經成為全球嚴重的健康問題，糖尿病腎病變的預防與治療是極為重要的議題。研究中藥治療糖尿病腎病變，進而開發成複合性保健食品有助於降低糖尿病腎病變發生率。高糖產生的活性氧化物(Reactive oxygen species, ROS)在腎臟引發氧化壓力是造成糖尿糖腎病變的重要因子，高糖造成的氧化壓力會刺激腎臟細胞分泌乙型轉型生長因子(transforming growth factor-β, TGF-β)，促使腎臟細胞產生更多ROS，並且增加腎臟細胞對TGF-β的反應性，造成腎臟細胞分泌細胞外間質(extracellular matrix, ECM) 蛋白，引發腎臟纖維化，降低腎功能；骨誘導蛋白-7 (bone morphogenetic protein-7, BMP-7) 是一個具有腎臟保護功能的蛋白，BMP-7協助維持腎臟細胞正常生理功能以及腎臟組織結構之完整性， BMP-7在初期糖尿病腎病變就會逐漸消失。增加糖尿病大鼠腎臟組織中BMP-7蛋白表現，有助於降低糖尿病腎病變的腎臟氧化壓力，進而抑制糖尿病腎臟中的TGF-β分泌以及ECM蛋白合成。中藥方劑小柴胡湯在保肝、抗發炎、抗腫瘤等研究中已有相當多報導，而此若以台灣特有種-高氏柴胡製備，則更能增加小柴胡湯的保肝及抗發炎功效，然而，高氏柴胡製備之小柴胡湯是否對糖尿病腎病變具有治療或保健功效卻無相關研究報告，因此，本研究將以高氏柴胡製備之小柴胡湯為材料，在動物實驗利用Streptozotocin (STZ)誘導糖尿病腎病變小鼠動物模型，體外細胞實驗利用高糖暴露之腎絲球細胞和腎小管上皮細胞模式，進行研究詳盡之研究，本計劃將評估高氏柴胡製備小柴胡湯對改善腎功能、抑制TGF-β以及ECM蛋白合成、提高腎臟保護蛋白BMP-7、及降低氧化壓力之效果，提出高氏柴胡製備小柴胡湯對改善糖尿病腎病變之證據，並且加上二十八天安全性評估與腎臟細胞安全性試驗。本研究藉由對於高氏柴胡製備小柴胡湯以及高氏柴胡本身之保護腎臟功能完整評估，可以證明其對於改善糖尿病腎病變之作用，未來可將此台灣特有之高氏柴胡進一步開發成具有保護糖尿病腎病變作用之中藥保健食品。
關鍵字：糖尿病腎病變、高氏柴胡、小柴胡湯、TGF-β、BMP-7、氧化壓力
Effect of Xiao-Chai-Hu-Tang prepared with Bupleurum kaoi on diabetic nephropathy
Ching-Hua Yeh
Institute of Medical Science, Chang Jung Christian University
Diabetic nephropathy (DN) is a serious health problem in the world. Preventions and therapeutics for DN are important health issues. Protect DN high risk patients from developing into nephropathy could decrease the incidence of DN. Oxidative stress is one of the factors leading to nephropathy which stimulates renal cells to secrete transforming growth factor-β (TGF-β) and promotes renal cells producing more ROS. Thus renal cells secrete extracellular matrix (ECM) protein which leads renal fibrosis and renal funciton impaired. Bone morphogenetic protein-7 (BMP-7) could maintain renal functions and renal structural integrity in kidney. BMP-7 may also counteract the fibrogenic activity of TGF-β in nephropathy. Many studies indicate that Traditional Chinese Medicine, Xiao-Chai-Hu-Tang (XCHT), with hepatoprotective, anti-inflammatory, anti-cancer ability. The bioactivities of XCHT remedy, prepared with Bupleurum Kaoi insteaded of Bupleurum chinense DC., could be enhanced. This study aims to clarify whether XCHT and B. Kaoi can prevent DN and whereby the mechanism in streptozotocin-induced diabetic mice and high-glucose exposed mesangial cells (RMC) and tubular epithelial cell (M1). We will analyze the ability of XCHT (B. Kaoi substituted) on decreasing TGF-β, and ECM, oxidative stress and increasing BMP-7 during the progression of DN in vivo and in vitro. We will also do the safety tests of these extracts in renal cells. The DN protective effect of XCHT and B Kaoi will be discovered. The results of study could be helpful on TCM-containing health food development.
關鍵字：Diabetic nephropathy ; Bupleurum Kaoi; Xiao Chai Hu Tang; TGF-β; BMP-7 ; oxidative stress
