Kaur Tajpreet, Kaur Anudeep, Singh Manjinder, Buttar Harpal Singh, Pathak Devendra, Singh Amrit Pal
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India; Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, India.
Eur J Pharmacol. 2016 Apr 15;777:96-103. doi: 10.1016/j.ejphar.2016.02.066. Epub 2016 Mar 2.
The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats.
本研究调查了肥大细胞向肾组织的浸润情况，以及肥大细胞稳定剂对高脂饮食（HFD）诱导的大鼠肾损伤的预防作用。连续12周给动物喂食HFD（30%脂肪）以诱导肾损伤。通过计算肥胖指数、脂肪量指数以及评估血浆中的总胆固醇、甘油三酯和高密度脂蛋白来评估HFD诱导的肥胖。通过测量肌酐清除率、血尿素氮、尿酸、电解质和微量蛋白尿来评估肾功能障碍。通过髓过氧化物酶活性、硫代巴比妥酸反应性物质、超氧阴离子生成和还原型谷胱甘肽水平来测定肾组织中的氧化应激。使用无创血压测量仪监测收缩压（SBP）。对肾组织中的组胺和羟脯氨酸含量进行定量。通过组织病理学确定肾组织中的大体组织病理学变化、肥大细胞密度和胶原沉积。每天给予肥大细胞稳定剂色甘酸钠和酮替芬，持续12周。喂食HFD的大鼠脂质水平显著升高，肾损伤伴肾氧化应激、SBP、肥大细胞密度、组胺含量和羟脯氨酸含量显著增加，而色甘酸钠和酮替芬治疗可减轻这些变化。因此，本研究的新发现表明，HFD诱导肥大细胞浸润到肾组织似乎在肾脏病理中起重要作用，用肥大细胞稳定剂治疗可作为治疗HFD诱导的大鼠肾功能障碍的潜在疗法。
