Zhou Ji-yin, Zhou Shi-wen
Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University of PLA, Chongqing 400037, China.
Yao Xue Xue Bao. 2007 Dec;42(12):1243-9.
Retinopathy is a major cause of morbidity in diabetes and remains the primary cause of new blindness. Therefore, it is necessary to find new drug to treat diabetic retinopathy. Type 2 diabetes mellitus (T2DM) rats were induced by injection (ip) with streptozotocin (STZ) 35 mg x kg(-1) and fed with a high-carbohydrate/high-fat diet 2 weeks later. From week 17 to 32, diabetic rats were given different doses of berberine 75, 150, and 300 mg x kg(-1), fenofibrate 100 mg x kg(-1) and rosiglitazone 4 mg x kg(-1), separately. Retinal structure was observed with hematoxylin-eosin staining and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma protein expressions were detected by immunohistochemistry. The retina of control rats was thicker than that of other groups, 16 weeks treatment with berberine (150 and 300 mg x kg(-1)) and rosiglitazone 4 mg x kg(-1) thickened the diabetic retina, but no difference existed in retinal structure among groups. Both berberine (150 and 300 mg x kg(-1)) and rosiglitazone 4 mg x kg(-1) significantly decreased PPARy expression in diabetic retina; while berberine (150 and 300 mg x kg(-1)) and fenofibrate 100 mg x kg(-1) obviously increased both PPARalpha and PPARdelta expressions in diabetic retina. Berberine modulates PPARalpha/delta/gamma protein levels in diabetic retina which may contribute to ameliorate retinopathy complication induced by STZ and a high-carbohydrate/high-fat diet. It is expected that berberine might be a more beneficial drug to treat diabetic retinal complication comparing with fenofibrate and rosiglitazone.
视网膜病变是糖尿病患者发病的主要原因，并且仍然是导致失明的首要原因。因此，有必要寻找治疗糖尿病视网膜病变的新药。通过腹腔注射35mg/kg链脲佐菌素（STZ）诱导2型糖尿病（T2DM）大鼠，两周后给予高碳水化合物/高脂肪饮食。从第17周开始至32周，分别给予糖尿病大鼠不同剂量的黄连素（75、150和300mg/kg）、非诺贝特（100mg/kg）和罗格列酮（4mg/kg）。采用苏木精-伊红染色观察视网膜结构，通过免疫组织化学检测过氧化物酶体增殖物激活受体（PPARs）α/δ/γ蛋白表达。对照大鼠的视网膜比其他组厚，黄连素（150和300mg/kg）和罗格列酮（4mg/kg）治疗16周使糖尿病视网膜增厚，但各组视网膜结构无差异。黄连素（150和300mg/kg）和罗格列酮（4mg/kg）均显著降低糖尿病视网膜中PPARγ的表达；而黄连素（150和300mg/kg）和非诺贝特（100mg/kg）明显增加糖尿病视网膜中PPARα和PPARδ的表达。黄连素调节糖尿病视网膜中PPARα/δ/γ蛋白水平，这可能有助于改善由STZ和高碳水化合物/高脂肪饮食诱导的视网膜病变并发症。与非诺贝特和罗格列酮相比，预计黄连素可能是治疗糖尿病视网膜并发症更有益的药物。
