Effect of berberine on the brain damage of glycated rats induced by D-galactose
- VernacularTitle:小檗碱对D-半乳糖诱导糖基化模型大鼠脑损害的干预作用
- Author:
Yuan LIN
;
Shiping ZHANG
;
Junhua Lü
- Publication Type:Journal Article
- From:Chinese Journal of Tissue Engineering Research
2006;10(43):200-203
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: As the damage caused by protein glycation is one of the mechanisms of diabetes, it is helpful to treat diabetes related diseases with the understanding of the inhibition of berberine on protein glycation and the protection to the brain damage caused by protein glycation.OBJECTIVE: To observe the effects of berberine on glycated brain damages induced by D-galactose in model rats.DESIGN: Randomly grouping paralleled control study.SETTING: Department of Ophthalmology, Xiamen Traditional Chinese Medicine Hospital.MATERIALS: The experiment was conducted in the Department of Pharmacology, Pharmacy College of Jinan University from June to October 2005. Ninety SD rats (6 weeks old) were selected and divided into 6 groups: control group, model group, hydrochloride aminoguanidine group and high (300 mg/kg), middle (150 mg/kg) and low (75 mg/kg) doses berberine groups with 15 rats in each group. The glycated models were established by intraperitoneal injection of D-galactose. The main drugs:berberine was from Guangzhou Wanji Drugs Limited Company; D-galactose was from Shanghai Yuanju Bioscience Technology Limited Company.METHODS: The rats in the control group were intraperitoneally injected the normal saline for 8 weeks; rats in other groups were injected 5%D-galactose (150 mg/kg) for 8 weeks. From the 3rd week, the hydrochloride aminoguanidine group was infused hydrochloride aminoganidine (150 mg/kg); the three doses berberine groups were given corresponding doses berberine; the control group and model group were given distilled water for 6 weeks with the volume of 10 mL/kg. At the end of the 8th week, the erythrocyte aldose reductase activity was determined by coomassie brilliant blue method; the level of plasma glycohemoglobin was measured by thio-barbituric acid colorimetry and the fructosamine in serum was measured by nitroblue tetrazolium colorimetry. The quantity of advanced glycation end products (AGEs) in serum, and AGEs, malondialdehyde (MDA), and activity of superoxide edismutase (SOD) in brain tissue and calcium ion in neurons were also dertermined. Moreover, the changes of mitochondria in brain hippocampus cells were observed under electronic microscope.MAIN OUTCOME MEASURES: ① The AGEs, plasma glycohemoglobin, serum fructosamine and aldose reductase activity. ②AGEs in brain tissues. ③Calcium level in brain. ④MDA content and SOD activity in brain tissues. ⑤Changes of mitochondria in hippocampus neurons.RESULTS: All 90 animals were involved in the result analysis. ①Aldose reductase activity and glycated product content in serum: After the rats were treated with D-galactose for 8 weeks, the aldose reductase activity in red blood cells and the content of fructosamine in serum, glycohemoglobin,AGEs in the model group were significantly higher than those in the normal control group (P ＜ 0.01); After treated by high and middle doses berberine for 6 weeks, the activity of aldose reductase and content of fructosamine in serum (absorbancevalue of hemoglobin every 10 g), glycohemoglobin, and AGEs were obviously lower than those in the control group [(1.07±0.39), (1.22±0.47), (1.76±0.30) nkat/g, t=5.052, 5.484, P ＜ 0.01;(0.740±0.142), (0.862±0.131), (0.958±0.083) mmol/L, t=7.829, P ＜ 0.01,t=2.404, P ＜ 0.05; 58.434±12.135, 64.614±13.418, 83.747±7.990,t=4.922, 6.748, P ＜ 0.01; (3.104±0.814), (2.937±0.514), (4.156±0.860) U/mg,t=4.104, 3.440, P ＜ 0.05]; the aldose reductase activity of the low dose berberine group was lower than the model group (P ＜ 0.05), which had no obvious effect on glycated products. ②AGEs in brain tissues: The contents in the hydrochloride aminoganidine group, high and middle doses berberine groups were lower than the model group [(10.52±1.22), (10.95±1.75),(11.95±2.27), (14.26±3.51) U/mg, t=-3.892, -3.263, P ＜ 0.01, t=-2.139,P ＜ 0.05], and the low dose berberine had little effect (P ＞ 0.05). ③Calcium level in neurons: The levels in the hydrochloride aminoganidine group,and high dose berberine groups were lower than the model group.[(271.52±32.71), (293.84±31.58), (337.15±58.49) nmol/L, t=-3.421, P＜ 0.01, t=-2.275, P ＜ 0.05], the low dose berberine group had no obvious effect (P ＞ 0.05). ④MDA content and SOD activity in brain tissues: MDA contents in the hydrochloride aminoganidine group, high and middle doses berberine groups were lower than the model group, and the SOD activity was markedly higher than the model group [(2.09±0.16), (2.12±0.22),(2.41±0.12), (2.54±0.21) μmol/g, t=6.601, 5.348, P ＜ 0.01, t=2.082, P＜ 0.05; (8.79±1.09), (8.80±1.52), (7.90±1.48), (6.48±1.34) mkat/g, t=4.571,4.254, P ＜ 0.01, t=2.226, P ＜ 0.05]. ⑤Mitochondria structure in brain hippocampus cells: Under the electronic microscope, mitochondria in brain hippocampus cells of the model group appeared obvious swelling with broken crests and disorganized structure, even obvious big vacuoles were observed. In the hydrochloride aminoganidine, and high and middle doses berberine groups, no obvious swelling was observed with vacuoles only in a few mitochondria. Nevertheless, obvious swelling appeared in mitochondria of low dose berberine group with broken crest and disorganized structure,and vacuoles were observed.CONCLUSION: D-galactose-induced damage in mitochondria may be related to AGEs formation in brain tissue, maladjustment of calcium ions in neurons and oxidative stress in rat models. Berberine can inhibit glycation induced by D-galactose and protect rat brain tissues from glycated damage.
