Krzyżewska Anna, Baranowska-Kuczko Marta, Galicka Anna, Kasacka Irena, Mińczuk Krzysztof, Kozłowska Hanna
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, 15-222, Poland.
Department of Clinical Pharmacy, Medical University of Białystok, Białystok, 15-222, Poland.
Pharmacol Rep. 2024 Apr;76(2):424-434. doi: 10.1007/s43440-024-00579-4. Epub 2024 Mar 22.
Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH.
The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg).
Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6.
The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.
肺动脉高压(PH)可导致右心室(RV)衰竭及随后的心肺肝综合征,即充血性肝病(CH)。肝脏中的被动淤血会影响炎症、纤维化,最终导致肝硬化。大麻二酚(CBD)具有多种有益特性,包括抗炎作用,且能降低大鼠由野百合碱(MCT)诱导的肺动脉高压中的右心室收缩压和右心室肥厚。因此,提示CBD可能有潜力限制继发于右心室衰竭的充血性肝病的发展。本研究旨在确定长期给予CBD是否能抑制继发于与MCT诱导的肺动脉高压相关的右心室肥厚的充血性肝病。
实验涉及有和没有MCT诱导的肺动脉高压的大鼠。在注射MCT(60mg/kg)后,每天给予CBD(10mg/kg)或其溶媒,持续3周。
给予野百合碱增加了肝/体重比。在组织学检查中,我们观察到肝细胞坏死和空泡变性以及窦状隙充血。在生化研究中,我们观察到核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)和白细胞介素6(IL-6)水平升高。给予肺动脉高压大鼠CBD降低了肝/体重比,改善了肝脏结构,并抑制了坏死的形成。大麻二酚还降低了NF-κB、TNF-α、IL-1β和IL-6的水平。
研究表明,CBD可能通过减轻肺动脉高压、对右心室的保护作用以及可能通过调节NF-κB途径对肝组织产生直接抗炎作用,从而保护肝脏免受充血性肝病的影响。