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Фармакологично Проучване На Поведенчески Ефекти На Chaenomeles Maulei При Експериментални Животни

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Фармакологично Проучване На Поведенчески Ефекти На Chaenomeles Maulei При Експериментални Животни МЕДИЦИНСКИ УНИВЕРСИТЕТ ВАРНА КАТЕДРА ПО ФАРМАКОЛОГИЯ И КЛИНИЧНА ФАРМАКОЛОГИЯ И ТЕРАПИЯ Весела Ангелинова Борисова-Ненова ФАРМАКОЛОГИЧНО ПРОУЧВАНЕ НА ПОВЕДЕНЧЕСКИ ЕФЕКТИ НА CHAENOMELES MAULEI ПРИ ЕКСПЕРИМЕНТАЛНИ ЖИВОТНИ ДИСЕРТАЦИОНЕН ТРУД За присъждане на образователна и научна степен „ДОКТОР“ по научна специалност „Фармакология (вкл. фармакокинетика и химиотерапия)“ Научен ръководител проф. д-р Стефка Василева Вълчева-Кузманова, д.м.н Варна, 2020 година Съдържание I. ВЪВЕДЕНИЕ ...................................................................................................................................... 6 II. ЛИТЕРАТУРЕН ОБЗОР ................................................................................................................. 9 1. Обща характеристика на видове от род Chaenomeles ............................................................... 9 1.1. Ботанически данни ...................................................................................................................... 9 1.2. Таксономия и номенклатура .................................................................................................... 10 1.3. Исторически преглед ................................................................................................................ 11 1.4. Състав на видове от род Chaenomeles ..................................................................................... 12 1.5. Съдържание на биологично активни вещества в плодов сок от Chaenomeles maulei ........ 15 2. Фармакокинетична характеристика на биологично активни вещества от плодов сок на Chaenomeles maulei .............................................................................................................................. 23 2.1. Резорбция на флавоноиди ......................................................................................................... 23 2.2. Резорбция на процианидини .................................................................................................... 23 2.3. Резорбция на фенолни киселини ............................................................................................. 24 2.4. Бионаличност на флавоноиди в мозъка .................................................................................. 26 2.5. Бионаличност на процианидини в мозъка .............................................................................. 27 2.6. Бионаличност на фенолни киселини в мозъка ....................................................................... 28 3. Депресия и депресивно-подобни симптоми - патогенетични механизми ........................... 30 4. Тревожност - патогенетични механизми ................................................................................... 39 5. Връзка между невродегенеративните и психиатричните заболявания .............................. 43 6. Антиоксидантни и психофармакологични ефекти на биологично активните вещества в род Chaenomeles ................................................................................................................................... 46 6.1. Психофармакологични ефекти на флавоноиди ...................................................................... 46 6.2. Антиоксидантни свойства на флавоноиди.............................................................................. 49 2 6.3. Психофармакологични ефекти на проантоцианидини .......................................................... 51 6.4. Антиоксидантни свойства на проантоцианидини .................................................................. 52 6.5. Психофармакологични ефекти на фенолни киселини ........................................................... 53 6.6. Антиоксидантни свойства на фенолни киселини .................................................................. 55 6.7. Проучени досега ефекти на видовете от род Chaenomeles ................................................... 57 7. Обобщение на литературния обзор ............................................................................................. 63 III. ЦЕЛ И ЗАДАЧИ ............................................................................................................................ 66 IV. МАТЕРИАЛИ И МЕТОДИ ......................................................................................................... 67 1. Материали ....................................................................................................................................... 67 1.1. Експериментални животни ....................................................................................................... 67 1.2. Плодов сок от Chaenomeles maulei .......................................................................................... 67 2. Методи .............................................................................................................................................. 69 2.1. Метод за изследване на двигателната активност и изследователското поведение - тест открито поле (open field test, OFT) ...................................................................................................... 69 2.2. Методи за изследване на тревожността .................................................................................. 69 2.3. Метод за изследване на депресивно поведение - тест принудително плуване (forced swim test, FST) ................................................................................................................................................. 71 2.4. Метод за изследване на паметта - тест разпознаване на обект - object recognition test (ORT) ...................................................................................................................................................... 71 2.5. Биохимични методи .................................................................................................................. 72 2.6. Статистически методи .............................................................................................................. 73 V. СОБСТВЕНИ РЕЗУЛТАТИ И ОБСЪЖДАНЕ ........................................................................ 74 1. Ефекти на плодов сок от Chaenomeles maulei върху здрави/млади плъхове ...................... 74 1.1. Ефекти на плодов сок от Chaenomeles maulei в тест открито поле ...................................... 75 1.2. Ефекти на плодов сок от Chaenomeles maulei в тест за социално взаимодействие ............ 81 1.3. Ефекти на плодов сок от Chaenomeles maulei в тест повдигнат кръстосан лабиринт ........ 83 3 1.4. Ефекти на плодов сок от Chaenomeles maulei в тест за разпознаване на обект .................. 94 1.5. Ефекти на плодов сок от Chaenomeles maulei в тест принудително плуване ................... 101 1.6. Ефекти на плодов сок от Chaenomeles maulei върху чернодробна и бъбречна функция . 103 1.7. Обсъждане ефектите на плодов сок от Chaenomeles maulei при млади/здрави плъхове . 112 2. Ефекти на плодов сок от Chaenomeles maulei върху резерпин-индуцирана хипокинезия в плъхове ................................................................................................................................................ 127 2.1. Ефекти на плодов сок от Chaenomeles maulei в тест открито поле .................................... 128 2.2. Ефекти на плодов сок от Chaenomeles maulei в тест принудително плуване ................... 131 2.3. Ефекти на плодов сок от Chaenomeles maulei върху реагиращи с тиобарбитуровата киселина субстанции в мозък ............................................................................................................ 132 2.4. Обсъждане на ефектите на плодов сок от Chaenomeles maulei върху резерпин-индуцирана хипокинезия в плъхове ....................................................................................................................... 134 3. Ефекти на плодов сок от Chaenomeles maulei върху плъхове, подложени на нарушен светлинен денонощен ритъм (НДР) ............................................................................................... 138 3.1. Ефект на плодов сок от Chaenomeles maulei в тест открито после .................................... 138 3.2. Ефекти на плодов сок от Chaenomeles maulei в тест за социално взаимодействие .......... 141 3.3. Ефекти на плодов сок от Chaenomeles maulei в тест принудително плуване ................... 142 3.4. Обсъждане на ефектите на плодов сок от Chaenomeles maulei върху плъхове, подложени на нарушен светлинен денонощен ритъм (НДР) ............................................................................. 143 VI. ОБОБЩЕНА ДИСКУСИЯ ....................................................................................................... 148 VII. ИЗВОДИ ...................................................................................................................................... 152 VIII. ПРИНОСИ ................................................................................................................................ 153 IX. СПИСЪК НА ПУБЛИКАЦИИТЕ И УЧАСТИЯТА, СВЪРЗАНИ С ДИСЕРТАЦИОННИЯ ТРУД.....................................................................................................................................................154 Библиография .................................................................................................................................... 156 4 Използвани съкращения BDNF- brain derived neurotrophic factor (мозъчен невротрофичен фактор) COX-1 и COX-2- cyclooxygenase 1 and 2 (циклооксигеназа- 1 и 2) CREB- c.AMP response element-binding protein EECS- етанолен
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