Morphofunctional state of the uterine appendages in chronic inflammation and complex treatment using mud extract (experimental clinical study) Nevostruev Sergey Aleksandrovich. Method for modeling autoimmune oophoritis

The urgency of the problem. Chronic inflammatory diseases of the uterine appendages (CIAD), despite the success in the development of new methods of treatment and the widespread introduction of laparoscopy into practical medicine, continue to be one of the urgent problems of clinical practice [Kulakov V.I., 2001; Smetnik V.P., 2003; Henry-Suchet J., 2000]. Patients with inflammatory diseases of the uterine appendages account for 60-65% of all gynecological patients [Serov VN, 2003; Risser W.L., 2002]. CVID is a common cause of pelvic pain syndrome, infertility, miscarriage, ectopic pregnancies and, as a result, a large number surgical interventions [Veren J., 2002; Taylor R.C., 2001; Vilos G.A., 2002]. In this regard, it is of particular importance to improve the quality of treatment of patients with CVID with the use of complex, pathogenetically substantiated approaches [Savel'eva GM, 1997; Ross J.D., 2001].

In domestic and foreign literature, there are numerous data on the pathomorphogenesis of chronic inflammation in the uterine appendages [Kovalsky GB, 1996; Krasnopolsky V.I., 1998; Herschlag A., 2000; Furuya M., 2002]. However, the degree of involvement in the inflammatory process of the ovaries, the reversibility of morphological disorders in the uterine appendages against the background of CVD, the possibility of influencing the reparative processes in the ovaries and fallopian tubes remain the subject of discussion until now. There are single experimental studies devoted to this problem, but their results are often contradictory [Tikhonovskaya OA, Logvinov SV, 1999; Ordonez J.L., 1999; Leese H.J., 2001].

In modern conditions, with CVDPM, there are clear trends, on the one hand, to the use of minimally invasive methods of operational diagnosis and treatment, on the other hand, to the optimization of measures aimed at the rehabilitation of the functions of the organs of the female reproductive system [Strugatsky V.M., 2003; Cibula D., 2001; Ness R.B., 2002]. Achievements of recent years give grounds to consider the methods of physiotherapy as one of the most promising, given their possibility of differentiated and directed action on various parts of the pathogenesis of the disease, increasing adaptive capabilities with a minimal risk of developing adverse reactions [Bogolyubov V.M., 1998; Strugatsky V.M., 2002].

An undoubted reserve for optimizing the treatment of CVDPM is the use of natural therapeutic muds and preparations derived from them, which have the ability to regulate neurohumoral and immune processes, prevent and reduce dystrophic changes, and stimulate the regeneration of cellular elements [Arkhipova L.V., 1995; Strugatsky V.M., 2003].

At the Institute of Petroleum Chemistry, TSC SB RAS (Tomsk), a dry extract of silt sulfide mud was created, containing a complex of mineral salts, microelements, organic substances, which has a wide range medicinal properties: anti-inflammatory, analgesic, hepatoprotective, etc. [Saratikov AS, 2001; Vengerovsky A.I., 2002]. The use of the extract in acute inflammation of the uterine appendages has an anti-alterative, anti-exudative effect mainly due to the membrane-stabilizing antioxidant effect, which is expressed in a decrease in the concentration of lipid peroxidation products and catabolism of cell membrane receptors [Tikhonovskaya OA, 1998, 1999, 2000].

At the same time, the mechanisms and regularities of the therapeutic effect of the silt sulfide mud extract in CVID remain poorly understood.

Purpose of the study. To study the effect of the silt sulfide mud extract on the morphological and functional state of the uterine appendages in chronic inflammation in the experiment and evaluate its clinical effectiveness.

Based on the above, the purpose and objectives of the study were formulated.

1. To develop models of chronic inflammation of the uterine appendages with a pronounced proliferative component.

2. To study on the created models of chronic inflammation of the uterine appendages in experimental animals the nature, dynamics and sequence of changes in various tissue elements: epithelium, connective tissue stroma, blood vessels, generative and endocrine elements.

3. Evaluate the effect of electrophoresis of silt sulfide mud extract on the dynamics of the morphofunctional state of the oviducts and ovaries, the intensity of reparative processes on models of chronic inflammation and experimentally substantiate the possibility of using it in the complex treatment of chronic inflammation of the uterine appendages.

4. To develop a method for the treatment of women with chronic inflammatory diseases of the uterine appendages, including the implementation of pelophysiotherapy from the early stages after laparoscopy.

5. To analyze the effectiveness of the method of treating women with chronic inflammatory diseases of the uterine appendages according to immediate and long-term results.

Scientific novelty. Experimental models of chronic monocultural and aseptic inflammation of the ovaries and oviducts in white outbred mature female rats have been developed. In the experiment, the pathomorphogenesis in the uterine appendages in chronic inflammation was studied in detail, the role of various structural elements in the tissue mechanisms of inflammation of the oviducts and ovaries, the sequence and nature of pathological disorders were determined.

For the first time, it has been established that the silt sulfide mud extract reduces the atresia of the ovarian follicular apparatus initiated by inflammation, prevents the formation of fibro-sclerotic adhesive changes and promotes the regression of fibrous tissue by activating macrophages and fibroclasts and normalizing the processes of collagenogenesis and collagenolysis.

Clinically proven high efficiency electrophoresis of 1% solution of silt sulfide mud as a pathogenetically substantiated component of CVDPM therapy. For the first time in this pathology, a study was made of the dynamics of the hormonal function of the ovaries, the functional activity of the fallopian tubes under the influence of pelophysiotherapy. The data obtained prove that the electrophoresis of the extract, carried out in the early stages after laparoscopic organ-preserving interventions on the uterine appendages, has a stimulating effect on ovarian function, increasing the secretion of estrogens and progesterone; restores the functional activity of the fallopian tubes.

Practical significance. The developed models make it possible to perform preclinical trials of new methods of treating CVD.

As a result of the research, a pathogenetically substantiated method for the complex treatment of CVDPM using an extract of silt sulfide mud has been developed. The proposed method of treatment increases therapeutic efficacy by immediate and long-term results: reduces the frequency of relapses, prevents the formation of pelvic pain syndrome, tubal-peritoneal infertility, ectopic pregnancy.

The use of pelophysiotherapy in gynecological practice in non-resort conditions makes it possible to make the latter economically accessible to the general population and is of great socio-economic importance.

Defense provisions.

1. In the pathomorphogenesis of experimental chronic inflammation of the uterine appendages, regardless of the phlogogen, there are similar changes manifested by disorders of the microcirculatory bed, massive atresia of growing follicles, fibrous-sclerotic and adhesive processes. In the mechanism of tissue disorders, an important role is played by a violation in the collagen synthesis-collagenolysis system.

2. The use of an extract of silt sulfide mud in chronic inflammation of the uterine appendages in the experiment limits the increase in atresia of the ovarian follicles, accelerates the regeneration of the oviduct mucosa, normalizes hemodynamics in the microcirculatory bed, and contributes to the reverse development of fibrous-sclerotic and adhesive processes.

3. In the mechanism therapeutic effect pelotherapy on the uterine appendages in chronic inflammation in the experiment, one of the leading places belongs to the activation of macrophages and fibroclasts and the normalization of the processes of collagenogenesis and collagenolysis, the restoration of the ultrastructural organization of the hematofollicular barrier

4. Electrophoresis of a 1% solution of silt sulfide mud extract increases the effectiveness of complex treatment of chronic inflammation of the uterine appendages in women in terms of immediate and long-term results.

Implementation into practice. The results of the study are used in the educational process at the Department of Obstetrics and Gynecology of the Medical Faculty of the Siberian State Medical University on the topic "Inflammatory diseases of the pelvic organs"; at the Department of Histology, Embryology and Cytology of the Siberian State Medical University on the topic "Female reproductive system"; medical activity gynecological clinic of the Siberian State Medical University and the "Center for Women's Health" OOO MADEZ.

Approbation of work. The main results of the work were reported and discussed at the scientific and practical conference of students and graduate students "Health of youth - the health of the nation" (Tomsk, 1998), the final conference "Tatiana's Day" based on the results of the Russian competition for the best scientific work of students in 1998 in the section " Medical Sciences" (Moscow, 1999), conference "Modern problems of fundamental and clinical medicine"(Tomsk, 1999), at the School of Young Researchers "Achievements in molecular biology and the development of new effective methods for the treatment of human diseases" (Moscow, 1999), VI and IX Russian National Congresses "Man and Medicine" (Moscow, 1999, 2002), I, II, III International congresses of young scientists and specialists "Scientific youth on the threshold of the XXI century" (Tomsk, 2000, 2001, 2002), Russian scientific and practical conference "Topical issues of endoscopic surgery in gynecology and obstetrics "(Tomsk, 2001), VI International Scientific and Practical Conference "Quality is a strategy of the XXI century" (Tomsk, 2001), Russian scientific conference with the participation of the CIS countries "Actual problems of experimental and clinical morphology" (Tomsk, 2002), city scientific and practical conference dedicated to the 40th anniversary of the Central Scientific Research Laboratory

Siberian State Medical University "Modern Aspects of Biology and Medicine" (Tomsk, 2003), the Russian Conference "Actual Issues of Urogynecology" (Tomsk, 2003), meetings of regional scientific and practical societies of obstetrician-gynecologists and morphologists (Tomsk, 2003-2004).

The volume and structure of the dissertation. The dissertation is presented on 204 pages and consists of an introduction, literature review, own observations, discussion, conclusions and practical recommendations. The bibliographic index contains 422 sources, of which 250 are in Russian and 172 in foreign languages. The dissertation contains 16 tables, 4 photographs, 32 micrographs, 10 electron diffraction patterns, 5 graphs.

1. The developed experimental models make it possible to obtain chronic inflammation of the uterine appendages with a pronounced adhesive process in the ovaries and oviducts, they are distinguished by relative ease of reproduction and stability of the inflammatory process.

2. Chronic monocultural and aseptic inflammation of the uterine appendages in the experiment causes pronounced proliferation and fibro-sclerotic changes in the connective tissue in the ovaries and oviducts, a decrease in the content of primordial, growing and mature follicles, corpus luteum, increases their atresia.

3. Electrophoresis of a 1% solution of silt sulfide mud extract promotes regression of fibrotic changes caused by inflammation, a decrease in the specific volume of connective tissue and the severity of the adhesive process. The extract limits atretic processes in the ovaries and stimulates the growth, maturation of follicles and the formation of corpus luteum.

4. The activation of fibroclasts and macrophages, which regulate the processes of collagen synthesis and resorption, plays an important role in the tissue mechanisms of the antisclerotic action of the silt sulfide mud extract. The extract reduces inflammation-induced hemodynamic vascular disturbances and ultrastructural changes in the hematofollicular barrier.

5. Laparoscopy and early start of pelophysiotherapy in the postoperative period can improve the results of complex treatment of women with chronic inflammatory diseases of the uterine appendages.

6. The use of electrophoresis of a 1% solution of an extract of silt sulfide mud from 1-2 days after laparoscopy increases the effectiveness of the treatment of chronic inflammatory diseases of the uterine appendages in terms of immediate and long-term results: clinical recovery in the treatment of the developed method was noted in 91% of cases; the frequency of episodes of exacerbation and recurrence of the pelvic pain syndrome is reduced by 3 times, the restoration of reproductive function was achieved in 55% of patients.

1. Patients with CVDPM after laparoscopy are recommended to prescribe a course of electrophoresis of a 1% solution of an extract of silt sulfide mud from 1-2 days after the operation. The procedures are carried out according to the standard abdominal-sacral technique. Electrodes with an area of ​​200-300 cm are placed transversely on the sacrum (cathode) and above the pubis (anode). Hydrophilic pads are wetted with 1% extract solution. l

The current density is 0.03-0.06 mA/cm, the exposure time is 10-20 minutes. The course consists of 10-12 procedures carried out in the morning, daily, with compulsory rest within 1-2 hours after physiotherapy.

2. The criteria for the effectiveness of the treatment of CVDPM is the achievement in the shortest possible time after the therapy of the first and second levels of rehabilitation - clinical recovery (absence of subjective and objective signs of inflammation in conjunction with the normalization of the echoscopic picture) in combination with the restoration of the endocrine function of the reproductive system (according to the results of TFD and the level plasma sex steroid hormones). In the longer term, the effectiveness of the treatment is assessed by the absence of recurrence of the disease, the normalization of the data of computerized cymopertubation and the rehabilitation of the reproductive function of a woman - the onset of pregnancy (III level of rehabilitation). >

3. In the absence of pregnancy within 6-12 months after complex treatment, or repeated laparoscopy for CVID, it is recommended to plan pregnancy using assisted reproductive technologies.

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