Vpliv kanabidiola na sečni mehur miši z eksperimentalno sproženim intersticijskim cistitisom

Bernard, Špela (avtor), Kerec Kos, Mojca (mentor), Erman, Andreja (komentor)

Intersticijski cistitis (IC) je bolezen spodnjega dela sečil, za katero je značilno kronično vnetje sečnega mehurja, kronične bolečine v spodnjem delu trebuha, ki jih spremljajo kronična povečana frekvenca uriniranja tako podnevi kot ponoči. Klinični simptomi IC niso specifični in se pogosto prekrivajo z drugimi obolenji, zato je postavitev prave diagnoze običajno zapletena. Zaradi neznane patofiziologije IC je trenutna terapija zgolj simptomatska. Kanabidiol (CBD) je najpogostejši kanabinoid, ki ga najdemo v konoplji (Cannabis sativa L). Je eden pomembnejših farmakološko aktivnih kanabinoidov, ki se uporabljajo v medicini, saj deluje protivnetno in antioksidativno ter nima psihoaktivnih učinkov. CBD bi lahko bil zaradi svojega protivnetnega in antioksidativnega delovanja ter hkrati nizke sistemske toksičnosti potencialno možno zdravilo tudi za IC. Do sedaj so pozitivne učinke drugih kanabinoidov zabeležili na živalskih modelih z IC/BPS, kjer so kanabinoidi uspešno ublažili simptome tega eksperimentalno sproženega obolenja. Namen našega raziskovalnega dela je bil ugotoviti vpliv CBD na sečni mehur miši z eksperimentalno sproženim intersticijskim cistitisom. V ta namen smo s pomočjo različnih metod (svetlobna in elektronska mikroskopija, imunooznačevanje, qPCR, prenos western, TEU) analizirali vpliv CBD na strukturo, funkcijo in vnetje sečnega mehurja miši z IC. Mikroskopska analiza je pokazala, da CBD pozitivno vpliva na obnovo poškodovanega urotelija in ponovno tvorbo tesnih stikov, ki so ključni za vzdrževanje krvno-urinske pregrade. Z merjenjem TEU sečnih mehurjev smo ugotovili, da je barierna funkcija urotelija miši, ki so prejemale CBD manj oslabljena po delovanju CP in posledično manj občutljiva na delovanje PLL v primerjavi s skupino miši, ki je prejemala le CP. CBD deluje protivnetno na sečni mehur miši s sproženim CP, saj zmanjša edem v steni sečnega mehurja. Rezultati qPCR in prenosa western so pokazali, da CBD v vnetem sečnem mehurju zmanjša izražanje gena za CB1R in poveča količino CB2R v steni sečnega mehurja. Naši rezultati nakazujejo na morebitno možnost uporabe CBD kot zdravilne učinkovine za zdravljenje bolnic z IC, seveda bi bile za zanesljivejše zaključke potrebne nadaljnje raziskave na večjem številu živali ter zlasti natančne analize mehanizma delovanja CBD v sečnem mehurju na molekularni ravni.

• Jezik: Slovenski jezik
• Ključne besede: intersticijski cistitis (IC), kanabidiol (CBD), sečni mehur, mišji model
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2023
• PID: 20.500.12556/RUL-147406
• Datum objave v RUL: 05.07.2023

BERNARD, Špela, 2023, Vpliv kanabidiola na sečni mehur miši z eksperimentalno sproženim intersticijskim cistitisom [na spletu]. Magistrsko delo. [Dostopano 25 april 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=147406

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: The effect of cannabidiol on urinary bladder in mice with experimentally induced interstitial cystitis

Izvleček

Interstitial cystitis (IC) is a debilitating condition of the lower urinary tract defined as chronic inflammation of the urinary bladder, accompanied by chronic pelvic pain and various urinary symptoms, such as increased frequency of voiding and nocturia. The clinical symptoms of IC are not specific and often overlap with other diseases, so setting the correct diagnosis is often difficult. Due to the unknown pathophysiology of IC, current therapy is symptomatic. Cannabidiol (CBD) is the most common cannabinoid found in hemp (Cannabis sativa L). It is one of the most important pharmacologically active cannabinoids used in medicine, as it has an anti-inflammatory and antioxidant effect and has no psychoactive effects. Due to its anti-inflammatory and antioxidant activity and at the same time low systemic toxicity, CBD could potentially be a possible treatment for IC as well. So far, the positive effects of other cannabinoids have been recorded in animal models with IC/BPS, where cannabinoids have successfully alleviated the symptoms of this experimentally induced disease. The purpose of our research was to determine the effect of CBD on the urinary bladder in mice with experimentally induced interstitial cystitis. We analyzed the impact of CBD on the structure, function, and inflammation of the urinary bladder in mice with IC using various methods (light and electron microscopy, immunolabeling, qPCR, Western blotting, TEER). Microscopic analysis shew that CBD has a positive effect on the restoration of the damaged urothelium and the re-formation of tight junctions, which are crucial for the maintenance of the blood-urine barrier. By measuring the TEER of the urinary bladders, we found out that the barrier function of the urothelium in mice that received CBD was less weakened after the action of CP and consequently less sensitive to the action of PLL compared to the group of mice that received only CP. We shew that CBD has an anti-inflammatory effect on the bladder of mice with induced CP, as it reduces edema in the bladder wall. The results of qPCR and Western blotting shew that CBD in the inflamed bladder decreased CB1R gene expression and increased the amount of CB2R in the bladder wall. Our results indicate the possibility of using CBD as a medicinal agent for the treatment of patients with IC, of course, more reliable conclusions would require further research on a larger number of animals and a detailed analysis of the mechanism of action of CBD in the urinary bladder at the molecular level.

• Ključne besede: interstitial cystitis (IC), cannabidiol (CBD), urinary bladder, mouse model