Method of preventing post-resection hyperglycaemia in experiment

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to experimental surgery and concerns prevention of post-resection hyperglycaemia after pancreatectomy in experiment. For this purpose 96 hours before pancreatectomy suspension containing twenty-four-hour culture of pancreatic island cells of newborn piglets in concentration 2106 in 1 ml of medium is introduced into iliac region once.

EFFECT: method ensures complete insulin-independence of experimental animal after pancreatectomy due to selection of optimal number of introduced cells as well as time and place of their introduction.

1 tbl

 

The present invention relates to medicine, namely to experimental surgery and pathophysiology.

There are various methods for correction of disorders of carbohydrate metabolism.

So there is a method of correction of blood glucose level of the animal with experimental diabetes. The known method is as follows. Previously in experimental animals (rats) were simulated diabetes by introducing alloxan. Animals that have over 2 weeks after modeling diabetes glucose in the blood exceeded 350 mg%, was injected into the portal vein and liver parenchyma culture islet cells of the pancreas 16-20-week human fetuses of (Shumakov V.I., B. I. Shal'nev and other Xenotransplantation of cultures of islet cells of pancreas human fetuses of rats with experimental diabetes mellitus // bul. The experimental. Biol. The honey. - 1980. - No. 1 - p.48-50). In the observed reduction of blood glucose level to baseline during the entire study period (8-18 weeks).

The disadvantages of this method include a gradual reduction of blood glucose level in experimental animals, which caused the need for appropriate insulin therapy. Thus, in animals with intraportal transplantation of cultures of islet cells of reduction is their glucose levels occurred during the week, and in animals with intrahepatic transplantation in 8 weeks.

Closest to the proposed technical essence is a way of correction of disorders of carbohydrate metabolism in pancreatectomized dogs by transplantation of islets of Langerhans in the abdominal cavity (K.Edamura, S.Itakura, K.Nasu, Y.Iwami, H.Ogawa, N.Sasaki, H.Ohgawara. Xenotransplantation of porcine pancreatic endocrine cells to total pancreatectomized dogs // J.Vet.Med.Sci. 65(5): 549-556, 2003).

The essence of this method consists in the following. Three weeks after pancreatectomy into the abdominal cavity of dogs for the correction of post-resection hyperglycemia enter biocapsule containing islet cells of the pancreas of a pig at a concentration of 1.8106per kg weight of the animal.

For three weeks after pancreatectomy the blood glucose level was supported by the introduction of insulin. Subsequent transplantation of islet cells of the pancreas allowed to gradually reduce the amount of insulin to 56% from the original, but complete abolition of the hormone could not be reached. Reduced blood glucose levels were observed for 4-21 weeks, necessitating the introduction of additional doses of insulin.

The disadvantages of this method include the fact that none of the experimental animal was not reached insulinnezavisimom, because after transplantation otmechalos is only a temporary reduction in insulin requirements.

The task of the invention is to develop a way to prevent post-resection hyperglycemia after pancreatectomy in the experiment.

The technical result of the present proposal is to provide full insulinnezavisimom experimental animal after pancreatectomy.

The technical result is achieved by that conduct introduction islet cells of the pancreas of a pig into the abdominal cavity of the experimental animal.

Distinctive technique proposed method is that the xenotransplantation carried out for 96 hours before pancreatectomy.

The difference also lies in the fact that the transplantation of islet cells of the pancreas of the pig carried out once in the left iliac region of the experimental animal.

Distinctive technique proposed method is the introduction of the suspension containing the daily culture of islet cells of the pancreas of newborn piglets at a concentration of 2106in 1 ml of culture medium.

Comparative analysis of the proposed technical solutions to the prototype allows to make a conclusion on the conformity of the proposed technical solution the criteria of the invention of "novelty."

The inventive method provides for the achievement of the technical result, namely software in full is winantivirus animal after pancreatectomy during the experiment.

The authors of the proposed method is established that pre-xenotransplantation provides adaptation of the transplanted cells and their function.

The authors of the proposed method is empirically set a deadline for the introduction of islet cells - 96 hours before pancreatectomy. Experimental studies have shown that the maximum insulinproducing cell function occurs within 96 hours after transplantation.

The use of mist islet cells of the pancreas of a pig at a concentration of 2106in 1 ml of culture medium provides sufficient for this type of animal concentration produced hormones.

The content of the islet cells of the pancreas in the amount of 2106in 1 ml of culture medium provides sufficient hormone producing function for this type of animal.

The introduction of the graft in the left iliac region provides optimal conditions for the functioning of the transplanted cells in the postoperative period, as on the subsequent pancreatectomy main volume operations are performed in the right half of the abdomen.

The analysis of the known technical solutions showed no information about the influence of the distinctive features of the proposed method to achieve a technical result that allows the essential the present invention meets the criterion of "inventive step".

The method constituting the invention, intended for use in medicine, namely in experimental surgery. The possibility of its fulfillment is confirmed as described in the application techniques and equipment. Therefore, the claimed invention meets the condition of patentability "industrial applicability".

The proposed method is as follows. For 96 hours prior to surgery - pancreatectomy experimental animal (rabbit) in the peritoneal cavity, namely in the left iliac region once imposed, the suspension containing the daily culture of islet cells of the pancreas of pigs at a concentration of 2 x 106in 1 ml of culture medium.

The proposed method is illustrated by a specific example.

The experiment was carried out in 10 rabbits breed "Chinchilla" in the age of 6 months and weighing 2700-3000 grams.

The control group of animals was 6 rabbits who have had pancreatectomy and preliminary xenotransplantation was not conducted.

For 96 hours before pancreatectomy each experimental animal performed a single injection of graft in abdominal cavity in the amount of 1 ml as graft were used islet cells of the pancreas of newborn piglets, namely their daily cultural a concentration of 210 6.

Through 96 hours after xenotransplantation experimental animals was performed pancreatectomy.

Animals of the control group within one hour after pancreatectomy noted high hyperglycemia 26,2 (22,7-30,0) mol/l, which had a strong character. Through daily monitoring of the blood glucose level continued to be high of 23.7 (22,6-24,8) mol/l, despite ongoing insulin therapy at a dose of 0.4 u/kg Mortality of animals in the control group was 100% in the first day of the postoperative period.

Animals of the experimental group was observed within 14 days, they spent the determination of blood glucose level and subsequent measurement of morphological patterns.

Determining the level of glucose in the blood of animals was performed in the dynamics immediately after surgery and every hour during the first day. The blood glucose level was determined by glucometer "One tuch". The results are presented in the table below.

Table
The level of blood glucose in rabbits (n=10), mmol/l
1 hour2 hours3 hours5 hours6 hours7 hours 8 hours9 hours10 hours
18,519,220,718,616,413,510,68,46,8

Analysis of the results showed that all animals of the experimental group was observed gradual decrease and normalization of blood glucose without insulin injections for 10 hours after pancreatectomy.

The removal of animals from the experiment material was collected at 7 and 14 days post-resection period. All animals of the experimental group after 10 hours of the postoperative period, the blood glucose level was in the range 6.4 (5,8-7,4) mmol/l throughout the entire observation period (7-14 days), indicating that the functioning of the transplanted islet cells and the relief of post-resection hyperglycemia.

Thus, the proposed method allowed us to achieve 100%survival of experimental animals after pancreatectomy, while the mortality in the control group was 100%. Implementation of the proposed method allowed to prevent the development of post-resection hyperglycemia after pancreatico the AI and ensure full insulinnezavisimom animals throughout the experiment.

The way to prevent post-resection of hyperglycemia in the experiment, including the introduction of the islet cells of the pancreas of a pig into the abdominal cavity of the experimental animal, wherein the pre for 96 h to pancreatectomy in the left iliac region once imposed, the suspension containing the daily culture of islet cells of the pancreas of newborn piglets at a concentration of 2106in 1 ml of culture medium.



 

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