山茱萸环烯醚萜总苷对糖尿病大鼠肾皮质糖化终产物及其受体mRNA表达的影响

Inhibitory effect of HXMTZG on the deposition of advanced glycation endproducts (AGEs) and the role of downregulating RAGE mRNA transcription in the renal cortex in diabetes rats

目的 :探讨山茱萸环烯醚萜总苷 (HXMTZG)对糖尿病大鼠肾皮质糖化终产物 (AGEs)的抑制作用及其对肾皮质内AGEs受体 (RAGE)mRNA转录水平的影响。方法 :用STZ 60mg/kg一次性腹腔注射造成糖尿病大鼠 ,连续灌胃给药 12周 ,取右肾皮质测定其AGEs荧光强度以间接表示肾皮质内AGEs的含量 ;用RT PCR半定量方法体外扩增目的基因RAGE ,并以 β actin作为内参 ,比较肾皮质内RAGEmRNA的表达情况。结果 :模型组AGEs沉积显著增加 ,RAGE表达明显上调 ;而环烯醚萜总苷能减少AGEs在肾皮质的过度沉积 ,同时亦能显著抑制RAGE的过高表达。结论 :山茱萸环烯醚萜总苷能抑制糖尿病大鼠肾皮质AGEs的形成 ,使其受体mRNA表达水平下降 ,具有减轻糖尿病肾病变的作用。

AIM: Lercanidipine is a new vasoselective dihydropyridine calcium channel blocker with a short plasma half-life,long duration of action, and demonstrated cardioprotective properties. We hypothesized that it might be effective at attenuating the adverse impact observed on the coronary compartment and myocardium in the transition phase to heart failure in the UM-X7.1 cardiomyopathic (CM) hamster. METHODS: The effects of 4-month exposure to lercanidipine 3 and 10 mg/kg (daily oral administration) Were evaluated in 150-day-old CM hamsters and in agematched normal hamsters. Coronary reactivity (reactive hyperemia to 30-s coronary occlusion) and the response to the administration of acetylcholine (100 nmol/L) and sodium nitroprusside (1 μmol/L) were assessed monthly, using the isolated perfused heart model. The left ventricular chamber dilatation index and wall thickness, myocardial fibrosis and myocardial capillary density (papillary muscle) were estimated in selected subgroups at monthly intervals. RESULTS: High-dose lercanidipine had beneficial effects on coronary dysfunctions: at month 4 of the treatment period, reactive hyperemia to short duration ischemia was improved, as was the endothelium-dependent vasodilator response (acetylcholine=68％±16％vs 11％±5％ in untreated CM hamsters, P<0.05)and endothelium-independent vasodilator response (sodium nitroprusside=36％±5％ vs 22％±12％ in untreated CM hamsters,P<0.05). Capillary density averaged 10 879±474 capillaries per mm^2 in papillary muscle from normal hamsters; this value did not change over time in normal hamsters and was not affected during the transition phase to heart failure in CM hamsters. Lercanidipine preserved myocardial capillary density in these conditions. Chronic exposure to lercanidipine had no impact on myocardial remodeling observed in CM hamsters. CONCLUSION: Lercanidipine had a beneficial impact on the coronary compartment in the transition phase to heart failure in a model of dilated cardiomyopathy.