糖尿病大鼠皮肤的组织学改变及其对糖皮质激素药物经皮吸收的影响  

The histological changes of diabetic rats’ skin and the effects on the percutaneous absorption of glucocorticoid

作　　者：王琳[1] 李国锋[1] 胡文军[2] 朱晓亮[3] 熊璐琪[1] 邓朝辉[2] 

机构地区：[1]南方医科大学南方医院药材科,广东广州510515 [2]广州军区联勤部药品仪器检验所,广东广州510500 [3]南方医科大学南方医院皮肤科,广东广州510515

出　　处：《药学学报》2010年第1期114-119,共6页Acta Pharmaceutica Sinica

基　　金：广东省科技攻关资助项目(2008B060600068);广东省自然科学基金资助项目(00197662101126001)

摘　　要：探讨糖尿病大鼠皮肤改变及其对糖皮质激素药物氢化可的松经皮吸收的影响。Wistar雄性大鼠随机分成正常组及造模1周组(W1)、2周组(W2)、3周组(W3)和4周组(W4),每组6只,采用链脲菌素(STZ,40mg·kg?1)对大鼠进行糖尿病造模,取大鼠腹部皮肤进行体外透皮扩散实验,接收液为磷酸盐缓冲液(PBS,pH7.4),HPLC法测定接收液中的药物量,计算出药物渗透速率;将造模不同时间的大鼠皮肤组织做病理切片,进行HE染色并观察是否存在组织学差异。结果发现,正常组、W1、W2、W3和W4组的渗透速率分别为(2.39±1.25)、(3.22±1.72)、(3.02±1.89)、(3.63±2.02)和(5.00±3.36)μg·h?1·cm?2。造模4周组与正常组之间存在显著差异(P<0.05),其余各组之间均无显著性差异;皮肤组织学观察结果显示:造模1周时大鼠腹部皮肤改变并不明显,1个月时表皮有变薄的现象,2个月时这种现象变得尤为明显。与正常皮肤相比,患糖尿病后的皮肤能引起药物经皮透过性的增加,这与糖尿病后发生一定程度的皮肤组织学改变关系密切。因此,提示糖尿病患者在必要时需要调整经皮给药的剂量。To examine the histological changes of diabetic rats’ skin and the effects on the percutaneous absorption of hydrocortisone （HC, a glucocorticoid）, male Wistar rats were randomly divided into five groups： control group, diabetes one-week group （W1）, two-week group （W2）, three-week group （W3）, and four-week group （W4）, while each group contained 6 rats. Diabetes mellitus （DM） rat model was prepared with the method of streptozocin （STZ, 40 mg·kg-1） intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer （PBS, pH 7.4） was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats’ abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occured. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 ± 1.25, 3.22 ± 1.72, 3.02 ± 1.89, 3.63 ± 2.02 and 5.00 ± 3.36 μg·h-1·cm-2, respectively. There was significant difference between the control and the W4 group （P〈0.05）, but no significant differences were found between any other two groups （P〉0.05）. The tissue slices showed that compared to the normal rats’ skin, little changewas observed in one-week DM rats’ skin, but the skin of one-month DM rats’ skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats’ skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.

关 键 词：糖尿病 皮肤 氢化可的松 经皮吸收 

分 类 号：R943[医药卫生—药剂学]