Enea N A, Hollis T M, Kern J A, Gardner T W
Department of Biology, Pennsylvania State University, University Park 16802.
Arch Ophthalmol. 1989 Feb;107(2):270-4. doi: 10.1001/archopht.1989.01070010276036.
To test the hypothesis that histamine receptors mediate increased blood-retinal barrier permeability in experimental diabetes, 51 rats were made diabetic by streptozocin injection (65 mg/kg; jugular vein) and were held for four weeks. The seven animal groups were as follows: untreated controls; untreated diabetic rats; diabetic rats receiving diphenhydramine hydrochloride (Benadryl); diabetic rats receiving cimetidine hydrochloride (Tagamet); diabetic rats receiving diphenhydramine and cimetidine; diabetic rats receiving purified pork insulin (Iletin II); and diabetic rats receiving insulin and diphenhydramine. All treatments were given during the last week. Blood-retinal barrier permeability was assessed through measurement of the vitreous content of fluorescein isothiocyanate conjugated to bovine serum albumin (FITCBSA) after 20 minutes of FITCBSA circulation. Vitreous FITCBSA content of the diabetic group was 64% greater than control content. Diabetic rats treated with either diphenhydramine or diphenhydramine and insulin had respective decreases of 43% and 40% in vitreous FITCBSA content. The vitreous content of the diabetic group receiving insulin was lowered 37% below untreated diabetic values, while the vitreous FITCBSA content of the diabetic group receiving both insulin and diphenhydramine was reduced 63%. These data indicate that retinal histamine H1-receptor activation may be partially responsible for initial blood-retinal barrier leakage of macromolecules into the vitreous and that this abnormal leakage can be prevented both by diphenhydramine and by insulin. Histamine H1 receptors may play an important role in mediating increased blood-retinal barrier permeability in experimental diabetes.
为了验证组胺受体介导实验性糖尿病中血视网膜屏障通透性增加这一假说，通过颈静脉注射链脲佐菌素（65mg/kg）使51只大鼠患糖尿病，并饲养四周。七个动物组如下：未治疗的对照组；未治疗的糖尿病大鼠；接受盐酸苯海拉明（苯那君）的糖尿病大鼠；接受盐酸西咪替丁（泰胃美）的糖尿病大鼠；接受苯海拉明和西咪替丁的糖尿病大鼠；接受纯化猪胰岛素（胰岛素II）的糖尿病大鼠；以及接受胰岛素和苯海拉明的糖尿病大鼠。所有治疗均在最后一周进行。在异硫氰酸荧光素与牛血清白蛋白结合物（FITCBSA）循环20分钟后，通过测量玻璃体内FITCBSA的含量来评估血视网膜屏障的通透性。糖尿病组的玻璃体内FITCBSA含量比对照组高64%。用苯海拉明或苯海拉明与胰岛素治疗的糖尿病大鼠，其玻璃体内FITCBSA含量分别降低了43%和40%。接受胰岛素治疗的糖尿病组玻璃体内含量比未治疗的糖尿病组降低了37%，而同时接受胰岛素和苯海拉明治疗的糖尿病组玻璃体内FITCBSA含量降低了63%。这些数据表明，视网膜组胺H1受体激活可能部分导致大分子最初从血视网膜屏障渗漏到玻璃体内，并且这种异常渗漏可以通过苯海拉明和胰岛素来预防。组胺H1受体可能在介导实验性糖尿病中血视网膜屏障通透性增加方面起重要作用。
