Puerarin And Cholecystokinin Reverse Diabetic Cataract In Rats And Initial Exploration On Its Mechanism

Diabetic mellitus (DM) is a common endocrine metabolic disease, which is spreading over the world and severely damaging mankind's health. It is characterized by high glucose, influences many organs and systems of the human body and leads to many complications such as heart, brain, kidney, eyes, peripheral vascular and nerve diseases etc., which are the main reasons for a high disability and mortality rate in patients with DM. Diabetic cataract and diabetic retinopathy are the most common complications in eyes and diabetic cataract is the leading main cause of blindness. Therefore, to study diabetic cataract thoroughly is an important topic that needs to be solved urgently.Research on mechanism of diabetic cataract has made remarkable progress. The major views that are accepted today are, abnormal glucose metabolic pathway and oxidation stress theories. The later has become of more and more interest to both the domestic and international ophthalmologists and is widely accepted in the medical field. Traditional oxygen-free radical stress mechanism pays more attention to the role of hydrogen-peroxide (H2O2), nitric-oxide (NO) and superoxide-anion (O2－.), while the new theory points towards peroxynitrite (ONOO－ ), a product from rapid reaction of NO and O2－., this may be an important mediator of cytotoxicity in oxidation. To date, there are no any reports on lens oxidation by ONOO－ pathway. NO is a new signal molecule with multi-regulation function, while inducible nitric-oxide synthase (iNOS) is the major inhibition enzyme in production of NO. It is likely that NO may contribute to oxidation stress by developing many more powerful oxidative agents such as ONOO－. It was reported that over-production of NO plays a more important role in causing damage to the retina. Current information indicates that NO is formed in the lenses of human, rat and rabbit. However, the changes among NO, iNOS and ONOO－ during the formation process of diabetic cataract are still not clear. New research suggests that puerarin may decrease the diabetic blood glucose concentration with its powerful anti-oxidative properties. But until now, there has been no data to verify whether or not puerarin is also effective in the treatment of diabetic cataract. If it is effective, what are the mechanisms and the relationships of it with NO, iNOS and ONOO－? Cholecystokinin octapeptide-8 (CCK-8) is not only a stomach-intestine hormone but also a nerve peptide, distributing in stomach, intestine and central nerve system and has many physiological functions. Former studies in our department revealed that CCK-8 played a protective role in rat lungs. Then, can CCK-8 also contribute the same ability to lens epithelium cell (LEC)? In order to disclose the mechanism of oxidation stress in the process of cataract formation and offer the new theory and experiment data for prevention and treating cataract,we established diabetic cataract animal model of rats in vivo and in vitro to study the pathogenesis of ONOO－ during the formation of diabetic rat cataract and the antagnizing of puarerin and CCK-8, separately. 1 To establish diabetic rat and diabetic rat cataract in an animal model in vivo.Healthy, male, Seventy-two Sprague-Dawly (SD) rats (250g±10g) were divided equally into control and streptozotocin (STZ) groups, the STZ group rats were given peritoneal injection of STZ (dosage 45mg/kg bw) to establish a diabetic rat and diabetic rat cataract in an animal model. The blood glucose level of the diabetic rats were measured by blood samples taken from the rats' tail vein after three days given STZ and over (16mmol/L) of the blood glucose was regarded as successful diabetic animal model and arranged into two groups, control group and STZ group. At the same time, rats in both control and STZ groups were given peritoneal saline everyday. The rats' general condition, body weight, blood glucose and ocular examination in the two groups were taken separately at twenty, forty and sixty days, respectively. Through the period of twenty...