Geranylgeranylacetone Alleviates Cecal Ligation And Puncture Sepsis-induced Organ Injury In Rats

【Objective】To observe whether geranylgeranylacetone(GGA) could alleviate organ injury in a rat cecal ligation and puncture(CLP) sepsis model.【Methods】Forty-eight health adult male Sprague-Dawley(SD) rats weighting 250～300g were divided into 6 groups randomly (n=8). A group (sham group); B group (CLP model group); C group (before CLP, SD rats were pretreated with vehicle G(5% gum Arabic and 0.008% tocopherol solution) and vehicle Q(0.05% glycerol solution)); D group (before CLP, SD mice were pretreated with quercetin(QUE) and Vehicle G); E group (before CLP, SD rats were pretreated with Vehicle Q and GGA); F group (before CLP, rats were pretreated with QUE and GGA orderly).【Measurements】18h after CLP, rats were anesthetized, arterial blood was collected from right carotid,made arterial blood gas analysis and got the quantities of pH, PaO2, PaCO2 and lactate(Lac) to estimate the general conditions of rats; examined levels of glutamic-oxaloacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), blood urea nitrogen (BUN) and serum creatinine (sCr) in serum and evaluated the function of liver and kidney; got left lobe and calculated wet weight/dry weight (W/D) ratio to estimate the level of lung edema; heart, lung, liver, kidney and small intestine were separated and treated to observe the changes of fracture in tissues and cells under microscope. 【Results】Compared with B, C, D and F, in group E, the quantities of pH, PaO2, PaCO2 and Lac changed a lot (P<0.01, respectively), they were 7.345±0.013, 86.75±5.06, 34.63±3.023 and 4.63±3.02 respectively; levels of AST, ALT, BUN and sCr in serum all decreased significantly (P<0.01, respectively), the results were 127.25±19.29, 58.5±8.38, 17.85±3.48 and 54.25±11.92; W/D ratio was 4.292±0.171, which also decreased at a large extent (P<0.01, respectively). Compared A with E, each result had statistic differences (P<0.05, respectively), so they did in F and E (P<0.01, respectively). Observing each tissue fracture under microscope, cells arraying our-of-order seriously, cell fracture broken down dramatically and general cellular swelling and necrosis appeared in B, C, D and F. In contrary, rats in group E, being pretreated with GGA and VQ, had better integrality and continuity of tissue fracture, which were closed to sham group.【Conclusions】GGA could lighten cellular swelling and necrosis in heart, lung, liver, kidney and small intestine and alleviate organ functions significantly in rats CLP sepsis models, and QUE could reversed the protective effects of GGA partly; the mechanism may be inducing the expression level of heat shock proteins (HSPs) in organs.