Gireesh Gangadharan, Reas S Khan, Jobin Mathew, Paulose Cheramadathikudiyil Skaria
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin 682 022, Kerala, India.
J Ethnopharmacol. 2008 Mar 5;116(2):296-304. doi: 10.1016/j.jep.2007.11.036. Epub 2007 Dec 4.
In the present study we have investigated the changes in the total muscarinic and muscarinic M1 receptor ([(3)H]QNB) binding and gene expression in the cerebral cortex of streptozotocin (STZ) induced diabetic, insulin and aqueous extract of Aegle marmelose leaf treated diabetic rats.
Diabetes was induced in rats by intrafemoral injection of streptozotocin. Aegle marmelose leaves was given orally to one group of rats at a dosage of 1g/kg body weight per day for fourteen days. Blood glucose and plasma insulin level were measured. Muscarinic and Muscarinic M1 receptor binding studies were done in the cerebral cortex of experimental rats. Muscarinic M1 receptor gene expression was studied using real-time PCR.
Scatchard analysis for total muscarinic receptors in cerebral cortex showed that the B(max) was decreased significantly (p<0.001) in diabetic rats with a significant decrease (p<0.01) in the K(d) when compared to control group. Binding analysis of Muscarinic M1 receptors showed that B(max) was decreased significantly (p<0.001) in diabetic group when compared to control group. The K(d) also decreased significantly (p<0.01) when compared to control group. The binding parameters were reversed to near control by the treatment of diabetic rats with Aegle marmelose. Real-Time PCR analysis also showed a similar change in the mRNA levels of muscarinic M1 receptors.
The results showed that there is decrease in total muscarinic and muscarinic M1 receptors during diabetes which is up regulated by insulin and Aegle marmelose leaf extract treatment. This has clinical significance in therapeutic management of diabetes.
在本研究中，我们调查了链脲佐菌素（STZ）诱导的糖尿病大鼠、胰岛素及印度楝树叶水提取物处理的糖尿病大鼠大脑皮质中总毒蕈碱和毒蕈碱M1受体（[³H]QNB）结合及基因表达的变化。
通过股内注射链脲佐菌素诱导大鼠患糖尿病。一组大鼠每天按1g/kg体重的剂量口服印度楝树叶，持续14天。测量血糖和血浆胰岛素水平。在实验大鼠的大脑皮质中进行毒蕈碱和毒蕈碱M1受体结合研究。使用实时PCR研究毒蕈碱M1受体基因表达。
大脑皮质中总毒蕈碱受体的Scatchard分析表明，与对照组相比，糖尿病大鼠的B(max)显著降低（p<0.001），K(d)显著降低（p<0.01）。毒蕈碱M1受体的结合分析表明，与对照组相比，糖尿病组的B(max)显著降低（p<0.001）。与对照组相比，K(d)也显著降低（p<0.01）。用印度楝树治疗糖尿病大鼠后，结合参数恢复到接近对照水平。实时PCR分析也显示毒蕈碱M1受体的mRNA水平有类似变化。
结果表明，糖尿病期间总毒蕈碱和毒蕈碱M1受体减少，胰岛素和印度楝树叶提取物治疗可上调其表达。这在糖尿病的治疗管理中具有临床意义。
