Hepatic Expression of Endocannabinoid Receptors (CB1 and CB2) in Patients with Non-Alcoholic Steatohepatitis and Its Relationship with Metabolic Syndrome

Öz

The pathogenetic pathways in the progression from steatosis to NASH have not yet been fully elucidated. Recent studies reported that the endocannabinoid system has a role in a variety of steps during chronic liver disease. Endocannabinoids are endogenous lipid mediators with a mechanism of action through activating cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Stimulation of the CB1 receptors increases hepatic fatty acid synthesis. Expression of CB2 receptors in fatty liver may be indicative of their association with metabolic syndrome. The fact that the endocannabinoid system activates various metabolic functions in peripheral tissues suggests that this system may play a role in the treatment of various diseases. In this study, we examined whether metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are associated with expression of cannabinoid receptors. Fifty-four individuals with nonalcoholic steatohepatitis (NASH) and 17 with steatosis based on pathology reports of liver biopsies were included in the patient group. Forty individuals whose liver tissue samples revealed hemangioma, focal nodules and/or simple cyst, and liver areas and liver tissues that were normal in pathology reports were selected as the control group. The association between cannabinoid receptor-1 (CB-1R) and -2 (CB-2R) expression, determined immunohistochemically, and metabolic syndrome criteria and NAS score were determined. A comparison of control (n = 40), steatosis (n = 17)and NASH groups (n = 54) revealed a significant difference in CB-2R expression between patients with steatosis and patients withNASH. The expression of CB-2 receptor in the steatosis group was statistically significantly higher than in the NASH group (p = 0.017). But showed no significant difference in CB-2R expression between NAFLD and control groups (p = 0.924). In our study, it was determined thatCannabinoid receptors-2 (CB-2Rs) were expressed in the liver cells of all patients and the control groups. In addition, the expression of thesereceptors was found to be associated with various parameters such as arterial hypertension, obesity, hyperlipidemia and lobularinflammation.

Anahtar Kelimeler

• NAFLD
• CB-2 receptors
• metabolic syndrome
• CB-1 receptors

Non-Alkolik Steatohepatitli Hastalarda Hepatik Endokannabinoid Reseptör CB1 ve CB2 ekspresyonu ve Metabolik Sendromla İlişkisi

Öz

Steatozdan NASH’a progresyona sebep olan patojenik metabolik yolaklar tam olarak açıklığa kavuşmamıştır. Son dönemdeki çalışmalarda endokannabinoid sistemin kronik karaciğer hastalığı sürecinde pek çok basamakta rol oynayabileceği belirtilmiştir. Endokannabinoidler canlılarda, Cannabinoid reseptör 1 (CB1) ve Cannabinoid reseptör 2’yi (CB2) aktive ederek etkinliklerini gösteren endojen lipid mediyatörlerdir. Endokannabinoid sistemin kronik karaciğer hastalığı sürecinde pek çok basamakta rol oynayabileceği belirtilmiştir. CB1 reseptörlerinin uyarılması hepatik yağ asidi sentezini arttırdığı ve yağlı karaciğerde CB2 reseptörlerinin eksprese olduğunun gösterilmesi bu reseptörlerin metabolik sendromla ilişkili olabileceğinin göstergesi olabilir. Endokannabinoid sistemin periferik dokularda çeşitli metabolik fonksiyonları aktive etmesi, bu sistemin çeşitli hastalıkların tedavisinde rol oynayabileceğini düşündürmektedir. Bizim çalışmamızda metabolik sendrom ve Nonalkolik yağlı karaciğer hastalığıyla cannabinoid reseptörlerinin ekspresyonu arasında ilişki olup olmadığı belirlenmiştir. Karaciğer biyopsilerinin patolojisi raporu NASH olan 54; Steatoz olan 17 kişi hasta grubuna dahil edildi. Karaciğer doku örneklerinde hemanjiom, fokal nodüler hiperplazi, basit kist saptananların patoloji preperatlarındaki normal karaciğer alanları ve normal karaciğer dokusu olarak raporlanan 40 kişi kontrol grubu olarak seçildi. İmmunhistokiyasal olarak CB1 ve CB2 Reseptörleri ile boyanma olup olmadığı, boyanmanın metabolik sendrom kriterleri ve NAS skoru ile olan ilişkisi belirlendi. Kontrol (n=40), Steatoz (n=17) ve NASH grubu (n=54) CB2-R ekspresyonu açısından karşılaştırıldıklarında, Steatozlu hastalar ve NASH’li hastaların CB2-R ekspresyonu aralarında anlamlı farklılık saptandı. Steatoz grubunda CB-2 reseptörünün ekspresyonu, NASH grubuna göre istatistiksel olarak anlamlı şekilde daha fazlaydı (p= 0.017). Fakat NAYKH ve kontrol grubundaki hastaların CB2-R ekspresyonu yüzdeleri karşılaştırıldığında iki grup arasında CB2-R ekspresyonu arasında anlamlı farklılık yoktu (p= 0.924). Çalışmamızda Kannabinoid reseptörleri-2’nin (CB-2R'ler), tüm hastaların ve kontrol grubunun karaciğer hücrelerinde eksprese edildiği belirlenmiştir.Ayrıca bu reseptörlerin ekspresyonu, arteriyel hipertansiyon, obezite, hiperlipidemi ve lobüler inflamasyon gibi çeşitli parametrelerle de ilişkili saptanmıştır.

Anahtar Kelimeler

• NASH
• CB1 reseptörler
• CB2 reseptörler
• Metabolik sendrom

Kaynakça

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