连术消渴颗粒对2型糖尿病模型大鼠血清炎症状态、肝脏脂代谢、氧化应激及病理变化的影响

Effects of Lianzhu Xiaoke granule on serum inflammatory state,liver lipid metabolism,oxidative stress and pathological changes in type 2 diabetes model rats

目的探讨连术消渴颗粒对2型糖尿病模型大鼠血清炎症状态及肝脏脂代谢、氧化应激、病理变化的影响。方法选取72只8周龄健康SD雄性大鼠,高脂高糖饲料喂养联合链脲佐菌素(streptozotocin,STZ)45 mg/kg腹腔注射,诱导2型糖尿病动物模型。成模后连术消渴颗粒高剂量组、连术消渴颗粒中剂量组、连术消渴颗粒低剂量组分别给予连术消渴颗粒11.68 g/(kg·d)、5.84 g/(kg·d)、2.92 g/(kg·d);二甲双胍组给予盐酸二甲双胍片0.17 g/(kg·d);空白组及模型组给予相同体积纯净水灌胃,各组大鼠每日给药1次,连续给药30天。检测各组大鼠血清一氧化氮(nitric oxide,NO)、一氧化氮合酶(nitric oxide synthase,NOS)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、超氧化物歧化酶(superoxide dismutase,SOD)水平及肝组织匀浆甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、丙二醛(malondialdehyde,MDA)水平,并观察各组大鼠肝组织病理学变化。结果与空白组比较,模型组大鼠血清NO、NOS、TNF-α水平及肝组织匀浆TG、TC、MDA水平显著升高(P<0.01),血清SOD水平及肝组织匀浆GSH-Px水平显著降低(P<0.01),肝脏组织形态显示肝小叶结构散乱,肝细胞凝固性坏死、重度水肿,肝细胞索及肝窦排列无规律不规则,病理变化显著(P<0.01)。与模型组相比,连术消渴颗粒高剂量组可使大鼠血清NO、NOS、TNF-α水平及肝组织匀浆TG、TC、MDA水平显著降低(P<0.01),血清SOD水平及肝组织匀浆GSH-Px水平显著升高(P<0.01);连术消渴颗粒中剂量组可使大鼠血清NOS、TNF-α水平及肝组织匀浆TG、TC、MDA水平显著降低(P<0.01),血清NO水平降低(P<0.05),血清SOD水平及肝组织匀浆GSH-Px水平显著升高(P<0.01);连术消渴颗粒低剂量组可使大鼠血清NO、NOS、TNF-α水平及肝组织匀浆TG、MDA水平降低(P<0.05),肝组织匀浆TC水平显著降低(P<0.01),GSH-Px水平显著升高(P<0.01),血清SOD水平升高(P<0.05);连术消渴颗粒高剂量组大鼠肝脏病理变化显著改善(P<0.01),连术消渴颗粒中剂量组大鼠肝脏病理变化改善(P<0.05),连术消渴颗粒低剂量组大鼠肝脏病理变化有改善的趋势,差异无统计学意义(P>0.05)。结论连术消渴颗粒可能通过改善血清炎症状态、降低肝脏匀浆血脂水平和抑制氧化应激发挥防治2型糖尿病的作用。

Objective To investigate the effects of Lianzhu Xiaoke granule on serum inflammatory state,liver lipid metabolism,oxidative stress and pathological changes of type 2 diabetes model rats.Methods Seventy-two eight-week-old healthy male SD rats were selected and fed with high-fat and high-sugar diet combined with streptozotocin(STZ 45 mg/kg)intra-abdominal injection to induce type 2 diabetes animal model.After modeling,the Lianzhu Xiaoke granule high-dose group,the Lianzhu Xiaoke granule medium-dose group and the Lianzhu Xiaoke granule low-dose group were given 11.68 g/(kg·d),5.84 g/(kg·d)and 2.92 g/(kg·d),respectively.The rats in the metformin group were given metformin hydrochloride tablet 0.17 g/(kg·d);the blank group and the model group were given the same volume of pure water by intragastric administration,once a day for 30 days.The levels of nitric oxide(NO),nitric oxide synthase(NOS),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD)in serum and the levels of triglyceride(TG),total cholesterol(TC),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in liver tissues homogenate of rats in each group were detected,and the histopathological changes of liver in each group were observed.Results Compared with the blank group,The levels of NO,NOS,TNF-αin serum and TG,TC and MDA in liver tissue homogenate of the model group were significantly increased(P<0.01),while the levels of SOD in serum and GSH-Px in liver tissue homogenate were significantly decreased(P<0.01).The results of liver tissue morphology showed that the hepatic lobule structure was scattered,liver cells coagulated necrosis,severe edema,hepatocyte cords and hepatic sinusoidal arrangement were irregular,and the pathological changes were significant(P<0.01).Compared with the model group,in Lianzhu Xiaoke granule high-dose group,the levels of NO,NOS,TNF-αin serum and TG,TC and MDA in liver tissue were significantly decreased(P<0.01),while the levels of SOD in serum and GSH-Px in liver tissue were significantly increased(P<0.01).In Lianzhu Xiaoke granule medium-dose group,the levels of NOS and TNF-αin serum,TG,TC and MDA in liver tissue homogenate were significantly decreased(P<0.01),the level of NO in serum was significantly decreased(P<0.05),and the level of SOD in serum and GSH-Px in liver tissue homogenate were significantly increased(P<0.01).In Lianzhu Xiaoke granule low-dose group,the levels of NO,NOS,TNF-αin serum and TG and MDA in liver tissue were decreased(P<0.05),the level of TC in liver tissue was significantly decreased(P<0.01),the level of GSH-Px was significantly increased(P<0.01)and the level of SOD in serum was increased(P<0.05).The liver pathological changes of rats in the Lianzhu Xiaoke granule high-dose group were significantly improved(P<0.01),and those in the Lianzhu Xiaoke granule medium-dose group were improved(P<0.05).The liver pathological changes in the Lianzhu Xiaoke granule low-dose group showed a trend of improvement,with no statistical significance(P>0.05).Conclusion Lianzhu Xiaoke granule may play a role in the prevention and treatment of type 2 diabetes by improving serum inflammatory state,reducing serum lipid level in liver homogenate and inhibiting oxidative stress.