ABSTRACT
OBJECTIVE： To study on the effects of prophylactic administration of Ramulus mori polysaccharides （RMP） on inflammatory response of renal ischemia reperfusion injury （RIRI） model mice and to explore its possible mechanism. METHODS： Totally 60 C57BL/6 mice were randomly divided to sham operation group， model group， atorvastatin group （positive control， 15 mg/kg）， RMP low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg）. Except for sham operation group， RIRI model was induced in other 5 groups. 24 h before surgery， they were given relevant medicine intragastrically， once a day， for consecutive one week. 24 h after reperfusion， the mice were sacrificed. The serum levels of Scr and BUN were detected. The morphological changes of renal tissue were observed under optical microscope. The serum levels of IL-1β， IL-6， IL-10 and TNF-α were determined by ELISA. Western blot assay was used to determine the protein expressions of Toll-like receptor 4 （TLR4）， p38 mitogen-activation protein kinase （p38MAPK） and p-p38MAPK. RESULTS： Compared with sham operation group， the serum levels of Scr and BUN were significantly elevated in model group （P＜0.01）. RIRI led to typical inflammatory response of renal tissue， widespread renal tubular epithelial cell degeneration and necrosis， and inflammatory cells infiltration. Serum levels of IL-1β， IL-6， IL-10 and TNF-α were increased significantly （P＜0.01）. The protein expressions of TLR4， p38MAPK and p-p38MAPK were increased significantly in renal cortex （P＜0.01）. Compared with model group， serum levels of Scr and BUN were decreased significantly in administration groups （P＜0.05 or P＜0.01）. The pathological damage of renal tissue was improved in varying degrees， especially in the RMP medium-dose and high-dose groups. Serum levels of IL-1β and IL-6 were decreased significantly in administration groups （P＜0.05 or P＜0.01）. Serum levels of IL-10 were further increased in atorvastatin group and RMP high-dose group （P＜0.01）， and serum level of TNF-α was decreased significantly in atorvastatin group and RMP medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The protein expressions of TLR4 and p-p38MAPK in renal cortex were decreased significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS： RMP prophylactic administration can improve RIRI of mice， the mechanism of which may be associated with relieving the inflammatory response through inhibition of TLR4/p38MAPK signaling pathway.
ABSTRACT
Aim To investigate the influence of Ramu-lus mori polysaccharides ( RMP) on blood glucose and anti-oxidative effect in streptozotocin ( STZ )-induced diabetic mice .Methods Diabetic mice were induced by intraperitoneal injection with 120 mg? kg -1 STZ and were randomly divided into the following 5 groups with 20 animals per group: model group , valsartan group ( 20 mg? kg -1 ) , low-, medium-, high-dose (0.3,0.6,1.2 g? kg -1 ) of RMP groups.Other 20 normal mice were treated as normal control group .The mice were administered orally for 90 d.On 45 d of ad-ministration , the 24 h urine was collected through met-abolic cages for urine protein detection .Pathological changes of kidney tissues were observed through HE staining .The serum levels of urea nitrogen ( BUN) and creatinine ( Cr ) were detected by automatic biochemical analyzer; and the manganese superoxide dismutase (Mn-SOD), catalase(CAT), malonaldehyde(MDA) and mitochondrial respiratory chain complex Ⅰ,Ⅲac-tivity of kidney tissues were also determined .ELISA method was used to detect ROS content in renal cortex . The SIRT1 , FOXO1 and NF-κB protein expressions were analyzed by Western blot .Results Compared with model group, the FBG, microalbuminuria, BUN and Cr were decreased by RMP medication ( P <0.05).The activities of Mn-SOD, CAT and mitochon-drial respiratory chain complex Ⅰ,Ⅲ in RMP groups were enhanced , while MDA and ROS levels were re-duced. Moreover, the expressions of SIRT1 and FOXO1 were up-regulated by RMP , the expression of NF-κB was down-regulated ( P<0.05) .Conclusion RMP exerts renal protective effect through up-regula-ting the expressions of SIRT1 and FOXO1 in renal cor-tex , which may relate to the improvement of anti-oxida-tive capability .