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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 investigate the changes of the skin in diabetic rats and its effect on the transdermal absorption of glucocorticoid hydrocortisone. Wistar male rats were randomly divided into normal group and model group (W1), 2 weeks group (W2), 3 weeks group (W3) and 4 weeks group (W4) STZ, 40mg · kg -1). The rats were subjected to diabetes mellitus. The in vitro transdermal diffusion assay was performed on the abdominal skin of rats. The receiving solution was phosphate buffered saline (PBS, pH7.4), and the content of The amount of drug was calculated to calculate the rate of drug permeation; the rat skin tissue made at different times was made pathological sections, HE staining and observed for histological differences. The results showed that the permeation rates of normal group, W1, W2, W3 and W4 group 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. There was a significant difference between the 4-week model group and the normal group (P <0.05), and no significant difference was found between the other groups. The skin histological observation showed that the skin changes in the abdomen were not obvious , 1 month when the epidermis thinning phenomenon, 2 months when the phenomenon becomes more apparent. Compared with normal skin, skin suffering from diabetes can cause increased percutaneous permeability of the drug, which is closely related to a certain degree of histological changes of skin after diabetes. Therefore, it is suggested that diabetic patients need to adjust the dosage of transdermal drug when necessary.