Rhein Improves Sepsis Rats by Reducing Inflammatory Reaction and Regulating AQP2 Acute Renal Injury

Abstract

Background: Inflammation is a typical manifestation of sepsis related acute renal injury. AQP2 is considered to play an important role in renal fluid transport. This study aims to explore whether rhein has a protective effect on renal injury and its potential mechanism. Methods: A sepsis rat model of acute renal injury was established. 60 SD rats were randomly divided into control group, model group, high rhein (200mg/kg), medium rhein (100mg/kg), low dose rhein (50mg/kg) and dexamethasone group. Observe the general condition of rats and detect serum creatinine (Scr), blood urea nitrogen (BUN) and TNF -α, IL-1 β, IL-10 expression; H&E staining was used to observe the pathological morphology of rat kidney; Immunofluorescence method was used to detect the expression of AQP2 in renal tissue: Western Blot method was used to detect the changes of protein expression of AQP2, NF-KB, P-NF-KB, IKB-α,P-IKB-α in renal tissue. Results: Compared with the control group, the levels of serum Scr, BUN and TNF-α, IL-1 β,and the level of IL-10 was significantly increased. There were obvious swelling of renal tubules, necrosis and abscission of epithelial cells of renal tubules, edema of renal interstitium, infiltration of inflammatory cells and other pathological damages in renal tissues; Compared with the model group, the rat serum Scr, BUN levels, TNF-α, IL-1β and the level of IL-10 was significantly reduced, and the pathological damage of renal tissue was significantly reduced. Conclusion: Rhein can reduce the inflammatory reaction, increase the expression of AQP2, and improve the acute renal injury in septic rats.

Aquaporin Expression and Regulation in Clinical and Experimental Sepsis

“…Interestingly, in rats exposed to LPS, treatment with dexpanthenol increased AQP2 mRNA expression in kidney tissues through the silent information regulator 1 (SIRT1) signaling pathway [ 43 ]. Liu et al demonstrated that the downregulation of AQP2 protein expression in rats with LPS-induced kidney injury could be attenuated by rhein treatment, an anthraquinone utilized in Chinese medicine with anti-inflammatory, antioxidant, and hepatoprotective properties [ 42 , 80 ]. Pre-treatment with propofol has been demonstrated to protect LPS-exposed rats with sepsis-induced kidney injury from further renal complications by preventing the downregulation of AQP2 expression [ 44 ].…”

“…Table 3 lists the regulators of AQP expression and their effects on experimental sepsis progression. LPS-exposed rats Pre-treatment with increasing concentrations of soy isoflavone resulted in dose-dependent upregulation of AQP1 mRNA and protein, alleviating pulmonary edema and lung damage [37] LPS-exposed rats Hydrogen-rich saline reverses AQP1 mRNA and protein downregulation [38] LPS-exposed rats Selenium treatment resulted in the upregulation of AQP1 protein expression in the kidneys [39] CLP rats MEF2C treatment attenuated the progress of lung injury while upregulating AQP1 mRNA and protein expression [40] CLP rats Emodin pre-treatment significantly increased AQP1 mRNA and protein expression, suppressing sepsis-induced pulmonary apoptosis [26] LPS-exposed HPMECs Silencing HIF1A expression in LPS-induced cells attenuated AQP1 upregulation and regulated the cells' volume increase [41] AQP2 LPS-exposed rats Dexpanthenol increased AQP2 mRNA expression in kidney tissues through the SIRT1 signaling pathway [43] LPS-exposed rats Rhein treatment attenuated the downregulation of AQP2 protein expression in the kidneys [42] LPS-exposed rats Propofol pre-treatment protected the rats from further kidney complications by restoring AQP2 mRNA levels [44] AQP3 CLP rats Ss-31 treatment resulted in decreased protein expression of AQP3 and pulmonary vascular permeability [27] AQP4 LPS-exposed mice TGN-020 treatment resulted in downregulation of AQP4, suppression of inflammatory cytokine production, and better survival rates [75] AQP5 LPS-exposed mice Lipoxin A 4 presents a protective role in lung injury by upregulating AQP5 protein expression in lung tissue [47] LPS-exposed mice Fasudil upregulates AQP5 mRNA and protein levels while eliminating LPS-induced lung edema and preventing LPS-induced pulmonary inflammation [46] LPS-exposed mice Estradiol treatment pre-LPS exposure upregulated AQP5 mRNA and protein levels, reducing oxidative stress and inflammatory responses [36] LPS-exposed rats Hydrogen-rich saline reverses AQP5 mRNA and protein downregulation [38] LPS-exposed rats Pre-treatment with increasing concentrations of soy isoflavone resulted in dose-dependent upregulation of AQP5 mRNA and protein, alleviating pulmonary edema and lung damage [37] CLP rats…”