Semenko V.V. Pathogenetic substantiation of L-arginine use for the correction of endothelial dysfunction in diabetic retinopathy (clinical-experimental study). – Qualifying scientific work published as manuscript.
The dissertation research is dedicated to the solution of the urgent problem of modern ophthalmology - increase of treatment efficiency in patients with diabetic retinopathy by studying features of endothelial dysfunction development and clinical-experimental substantiation of its correction by L-arginine.
The experimental part was performed on white rats of the Wistar line of self-breeding, weighing 180-200 g. According to the tasks, the animals were divided into 3 groups: 1st group - 20 intact animals; 2nd group - 30 animals in which type 1 diabetes was modeled; 3rd group - 30 animals, which received 7.5 mg of arginine per 100 g of rats on the background of simulated diabetes. Diabetes mellitus was simulated by three intraperitoneal injections of alloxan at a dose of 7.5 ml / 100 g of animal weight with an interval of 5 days. The drug was administered on the background of free drinking of 5% fructose solution. The experiment lasted 30 days. We used the optimal dose of alloxan, which does not lead to the death of rats and is an effective model not only for the development of diabetes in general, but also for its microvascular complications in the form of diabetic retinopathy (DR), as evidenced by the results of our experiment. A study of the metabolic therapy with L-arginine effectiveness was carried out.
An important aspect of studying the diabetes influence on the development of DR is experimental modeling, when the breakdown in various tissues of the body revealed a violation of metabolism and function of nicotinamide coenzymes. Thus, in the study of moderate activity class in the ganglion layer of the eyeball revealed very relevant differences (p <0,001) between groups on the enzyme LDH. In the experimental group in a larger number of animals, this enzyme was in a moderate class of activity. Regarding the class of high enzyme activity, very significant differences (p <0.001) were found between the number of rats in the experimental group and the control, in which the activity of all three enzymes (LDH, LDH and MDG) was within this class.
As a result of our research at the background of DR modelling changes in blood vessels were found in the form of wall fibrosis, endothelial edema and vascular spasm. There was also a decrease in the number of pigment granules, dystrophic changes in the cells of the ganglion layer and the layer of rods and cones, which coincides with the descriptions of damage to the membranes of the eyeball in patients with diabetes. Correction of simulated diabetes with L-arginine helps to preserve the structure of blood vessels and the structure of the layers of the eyeball and helps to reduce the manifestations of the pathological process as a consequence. This increases the activity of NO-S and normalizes the studied biochemical markers of endothelial function compared with the diabetes without the use of L-arginine, and approaches the level of normal, which indicates an improvement in endothelial function. Restoration of balance of the pro- and antioxidant system under the influence of exogenous introduction of nitric oxide donors was also revealed.
The applied (hereinafter - clinical) study involved 108 patients (216 eyes) with a diagnosis of type 2 diabetes aged 45 to 60 years, including 56 men and 52 women. The aim of the clinical part of the study was to evaluate the effectiveness of L-arginine in patients with non-proliferative DR based on the analysis of clinical and biochemical parameters. Emmetropic refraction was observed in most patients (95 people - 88%). In 9 patients (8.3%), myopic refraction was determined: in 5 people - mild myopia, in 4 - moderate myopia. In 4 patients (3.7%) - hyperopic refraction of low level. Visual acuity of all patients was indicated with correction. The study involved patients with non-proliferative stage of mild DR without signs of clinically significant macular edema. There were statistically significant differences in the indicators of Willebrand factor, endothelin-1 and NO-synthase depending on the severity of DR by ETDRS (14, 15, 20 and 35 levels). The use of L-arginine revealed a statistically significant positive dynamics of the content of Willebrand factor, endothelin-1 and NO synthase (p <0.001), there is a probable improvement in glycosylated hemoglobin. The treatment with L-arginine also led to a decrease in blood pressure in patients and bringing them closer to normal.
The use of L-arginine allowed to stabilize the clinical course of DR, as evidenced by the lack of negative dynamics in patients on the background of this drug intake.
