Elattar Samah, Estaphan Suzanne, Mohamed Enas A, Elzainy Ahmed, Naguib Mary
Physiology Department, Faculty of Medicine Cairo University, Egypt.
Physiology Department, Faculty of Medicine Cairo University, Egypt.
J Steroid Biochem Mol Biol. 2017 Oct;173:235-244. doi: 10.1016/j.jsbmb.2016.11.012. Epub 2016 Nov 19.
There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH)D3. Altered 1α,25(OH)D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH)D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH)D3 (0.5μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH)D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH)D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH)D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH)D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFkB and PPAR-α. Both agents together had a synergistic effect.
越来越多的证据表明1α,25(OH)D3具有免疫调节作用。1α,25(OH)D3水平的改变可能在2型糖尿病的发生发展中起作用，并参与肝脏疾病的发病机制。我们的研究旨在研究和比较二甲双胍和补充1α,25(OH)D3对2型糖尿病大鼠肝损伤的影响。将60只雄性白化大鼠分为5组；第1组：对照大鼠。其余大鼠给予高脂饮食2周，然后腹腔注射链脲佐菌素（35mg/kg体重）诱导2型糖尿病，再分为：第2组：未治疗的糖尿病大鼠，第3组：用二甲双胍治疗的糖尿病大鼠（100mg/kg体重/天，口服），第4组：每周3次腹腔注射补充1α,25(OH)D3（0.5μg/kg体重）的糖尿病大鼠，第5组：同时补充1α,25(OH)D3和二甲双胍的糖尿病大鼠。8周后，测量血清葡萄糖和胰岛素水平，计算HOMA-IR，评估血脂、Ca2+、ALT和AST。取肝脏标本检测PPAR-α（脂质代谢调节因子）、NF-κB p65、半胱天冬酶3和PCNA（增殖细胞核抗原），并进行组织学检查。糖尿病大鼠的肝酶升高，组织学结果显示糖尿病对肝脏有损伤作用。与未治疗的大鼠相比，1α,2(OH)D3、二甲双胍以及两种药物联合治疗均显著改善了肝酶。这种改善与血糖控制、血脂和血清Ca2+的显著改善相关，与未治疗组相比，NF-κB p65和半胱天冬酶3显著降低，PPAR-α和PCNA表达增加。与二甲双胍相比，1α,25(OH)D3诱导的效果稍好。两种药物联合具有协同作用，几乎完全保护了肝脏。组织学结果证实了生化结果。我们的结果表明，1α,25(OH)D3和二甲双胍对糖尿病大鼠肝脏具有保护作用，表现为肝酶水平改善、细胞凋亡减少、增殖增加，组织学检查证实了这一点，同时调节了NF-κB和PPAR-α。两种药物联合具有协同作用。
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